UNITED STATES OF AMERICA
+ + + + +
THE PRESIDENT'S COUNCIL ON BIOETHICS
+ + + + +
+ + + + +
April 25, 2002
+ + + + +
The Council met at 8:30 a.m., in the Dewey
Rooms of the Hilton Crystal City, 2399 Jefferson Davis
Highway, Arlington, Virginia, Dr. Leon Kass, Chairman,
LEON R. KASS, M.D., PH.D., Chairman
ELIZABETH H. BLACKBURN, Ph.D., Member
REBECCA S. DRESSER, J.D., Member
DANIEL W. FOSTER, M.D., Member
FRANCIS FUKUYAMA, Ph.D., Member
MICHAEL S. GAZZANIGA, Ph.D., Member
ROBERT P. GEORGE, DPhil, J.D., Member
MARY ANN GLENDON, J.D., Member
ALFONSO GOMEZ-LOBO, J.D., Member
WILLIAM B. HURLBUT, M.D., Member
CHARLES KRAUTHAMMER, M.D., Member
PAUL MCHUGH, M.D., Member
GILBERT C. MEILAENDER, JR., Ph.D., Member
JANET D. ROWLEY, M.D., D.Sc., Member
MICHAEL J. SANDEL, D.Phil, Member
JAMES Q. WILSON, Ph.D., Member
Session 1: Stem Cells 1: Medical Promise
of Embryonic Stem Cell Research
(Present and Projected)
Dr. John Gearhart ................................. 10
Session 2: Stem Cells 2: Medical Promise
of Adult Stem Cell Research
(Present and Projected)
Dr. Catherine Verfaillie .......................... 88
Session 3: Stem Cells 3: Ethics of Human
Stem Cell Research
Dr. Gene Outka ................................... 171
Session 4: Human Cloning 10: Ethics of
Cloning for Biomedical Research .................. 247
Adjournment ...................................... 315
2 (8:43 a.m.)
3 CHAIRMAN KASS: Well, I would like to ask
4 Dean Clancy to officially open the meeting, please.
5 MR. CLANCY: This meeting is lawful.
6 DR. KASS: Thank you very much. Apologies
7 to our guests and to members of the audience for the
8 late start. Council Members had to take an oath of
9 office, which should have been administered to us
10 before our very first meeting.
11 That has been done and we are now legal in
12 every respect. Welcome to this, the third meeting of
13 the President's Council on Bioethics. We are
14 expecting colleagues Krauthammer and George today, and
15 Stephen Carter will not be with us, and Bill May will
16 join us tomorrow.
17 I would like to introduce a new member of
18 our staff, Judy Crawford, who comes to us as the
19 office manager. Judy, would you please rise so that
20 the council members can know you. We are very
21 delighted to have Judy with us.
22 We reconvene as the debate about the
23 cloning legislation heats up around us, a debate that
24 we did not begin and do not control. We are in the
25 midst of our own careful and thorough investigation of
1 the ethical, social, and policy implications of human
2 cloning seen in its larger scientific, medical, and
3 human contexts.
4 We have chosen to proceed in a deliberate,
5 collegial, wisdom-seeking, mode in keeping with our
6 charge to inquire fundamentally into the human and
7 moral significance of developments in biomedical
8 science and technology.
9 The most challenging aspect of our inquiry
10 to date has been the moral significance of cloning for
11 biomedical research, a topic discussed for the first
12 time at our last meeting, and to which we return later
13 today in the hope of making progress and clarifying
14 the contested moral issues at stake, and in
15 articulating the best possible moral arguments for and
16 again the conduct of such research.
17 On behalf of the council, I would like to
18 thank the staff for its superb work in advancing our
19 inquiry, and on behalf of the staff, I would like to
20 thank council members for their thoughtful comments
21 and responses. We are in your debt.
22 The agenda for this meeting brings us into
23 some new, but not altogether unrelated, areas of
24 inquiry. Stem cell research, a topic of our first
25 three sessions today.
1 Second, the question of therapy versus
2 enhancement as a goal for the uses of biomedical
3 technology, and third, possible regulation of
4 biomedical technology. These topics have been
5 selected with a view to initiating one of our
6 obligatory future projects, stem cell research, and
7 exploring two possible future projects for the council
8 for the rest of our two year charter.
9 As everyone knows, in his speech
10 announcing the creation of this council, President
11 Bush charged us with monitoring stem cell research,
12 embryonic and non-embryonic, human and animal, in
13 order to assess their progress in gaining knowledge
14 and beneficial therapies, and in due course to offer
15 guidelines and regulations for the conduct of such
17 As I indicated at our first meeting, we
18 have begun to collect data that will enable us to
19 describe, assess, and compare the successes achieved
20 with both embryonic and non-embryonic stem cells.
21 As we are doing this, however, it seemed
22 desirable for council members to learn firsthand, and
23 from some leading researchers in the field, about the
24 scientific and therapeutic promise of stem cell
1 research present and projected; embryonic and non-
3 And it also seemed desirable to explicitly
4 begin a disciplined conversation about the ethical
5 issues of embryonic stem cell research. Our first
6 three sessions today constitute the official thematic
7 beginning of our project on stem cell research.
8 We have of course already been
9 deliberating about some of these matters in our
10 discussion of human cloning for biomedical research, a
11 topic that first arose for us as a crucial side
12 question of the larger subject of human cloning to
13 produce children,
14 what to think about it, and what to do about it.
15 This is therefore a useful juncture at
16 which to indicate the distinction, as well as the
17 connection between these two topics. Many members of
18 the public, including many of our elected officials
19 who are in the process of making policy in this area,
20 as well as some members of the media, have conflated
21 the issue of stem cell research and the issue of
23 The issue of cloning comes first to
24 attention as an issue of the ethics of producing
25 children by novel technological means, and the issue
1 of cloning, insofar as it has captured the public
2 attention, is primarily about what to think about the
3 asexual production of new human beings who are going
4 to be genetically virtually identical to already
5 existing individuals.
6 And the issues there are in the first
7 instance the questions of the ethics of, crudely
8 speaking, baby-making. That is quite different from
9 the question of the ethics of embryo research.
10 Virtually all embryonic stem cell research
11 now under way, both in humans and in animals, involve
12 cell lines developed from embryos, whether inner-cell
13 mass, or from the gonadal ridge of donated fetuses,
14 that originate from the sexual union of egg and sperm,
15 and very often in the human case using excess embryos
16 produced in in vitro clinics and in all cases from
17 material not produced for the sake of the research.
18 The question of Federal funding of this research that
19 President Bush resolved last summer, this was the
20 question that was resolved last summer, and the
21 research in this area proceeds not only with Federal
22 funding under the guidelines that the President
23 established, but also in the private sector.
24 The two topics, however, intersect and
25 overlap because cloning to produce children
1 necessarily proceeds through the production of cloned
2 blastocysts, which offer special opportunities for
3 embryonic stem cell and other research.
4 Some proposals to curtail cloning for
5 providing children would do so by curtailing the
6 initial steps, thus interfering with the possibility
7 of using cloned embryos for research.
8 And this has given rise to arguments for
9 and against cloning for biomedical research proper.
10 This is where the intersection can be made explicit,
11 and that is where we now are.
12 In order for us in the other project to
13 continue to make progress, and therefore in order to
14 see what value added might derive from working with
15 embryonic stem cells extracted from cloned
16 blastocysts, one needs to know something about what it
17 would be added to. That is to say, to work on ordinary
18 embryonic stem cells. And in order to see more clearly
19 what the ethical issues are that might come from the
20 question of producing cloned embryos for biomedical
21 research, it would be helpful for us to know something
22 of the ethical issues of experimenting on human
23 embryos of sexual and not clonal origin, and of using
24 extra embryonic -- using the extra embryos or fetuses
25 not created for experimental purposes so we can see
1 what different questions arise here.
2 To help us with our scientific and medical
3 education, we are very fortunate to have as our guests
4 and presenters this morning two distinguished
5 researchers, one who is a pioneer in isolating and
6 characterizing human pluripotent stem cells, Dr. John
7 Gearhart, the C. Michael Armstrong Professor of
8 Medicine at Johns Hopkins University, and the Director
9 of the Institute of Cell Engineering.
10 And second a person who is a pioneer in
11 work with human multipotent adult progenitor cells,
12 Dr. Catherine Verfaillie, a Professor of Medicine and
13 Director of the Stem Cell Institute at the University
14 of Minnesota.
15 Each of our guests in separate sessions
16 will make formal presentations, roughly 30 to 35
17 minutes, after which time we will have a chance to ask
18 questions about the scientific, technological, and
19 clinical aspects of these areas of research.
20 This is our chance to learn about the
21 wonderful prospects of these investigations. However,
22 let me say that because our guests are here not only
23 as scientists, but also as our neighbors, in a morally
24 aspiring human community, we will perhaps try toward
1 the end to elicit from them their own thoughts about
2 the ethical issues in their own work.
3 But the purpose of these sessions is
4 primarily our own education about the scientific and
5 medical aspects. With that I would like to turn the
6 meeting over to Dr. Gearhart, and to thank him very
7 much for joining us this morning.
8 DR. GEARHART: I am certainly grateful to
9 have this opportunity to share with the President's
10 Council my knowledge in a very tiny area of biomedical
11 research, and it is currently quite tiny, but if you
12 read and believe the press, it is obviously going to
13 expand enormously.
14 Much has been written and much has been
15 said about stem cells, and it seems every morning in
16 the paper there is some article relating to it and
17 continuing the debate.
18 In the scientific literature, we see
19 virtually in every issue of leading journals a paper
20 dealing with stem cells. An age old dream I think of
21 mankind or humankind has been to replace damaged or
22 diseased tissues with functional ones, new ones, and
23 wouldn't it be nice to be able if you had a damaged
24 liver or kidney to take one off the shelf if you know
25 what I mean.
1 And this dream I think is going to become
2 a reality, and with some of the advances in biomedical
3 research, and one of the ones that we are going to
4 talk about today, I think this will provide the
5 starting material that will lead to this reality.
6 The concept behind cell-based therapies --
7 and this is what we are talking about here initially -
8 - is a very simple one, and I think that that makes it
9 attractive, and it makes it understandable to the
11 And that is that if there is a tissue
12 deficit, why not just replace the tissue. Now, it is
13 easy to say, and it will be difficult to do, but the
14 concept is an easy one.
15 Cell-based therapy has also been called
16 regenerative medicine, and there are many rubrics for
17 this today. The power of this technology is derived
18 from information inherent in our genes and in our
19 cells, and the recent isolation of these embryonic
20 type stem cells I believe is going to provide the
21 enabling material as I mentioned for this to go
23 Stem cells are going to serve several
24 purposes, the first of which could be as a direct
25 source in transplantation therapies. That means
1 specific cell types will be grown in culture, such as
2 heart muscles, nerves, et cetera, and transplanted to
3 patients for function.
4 Or they will be genetically engineered to
5 do exactly what we want them to do and transplant it
6 to patients; or they will be used by our tissue
7 engineer colleagues to construct tissues and parts of
8 organs, which would then be transplanted to patients.
9 Stem cells will also be used as a source
10 of information, basic science, and this is really
11 where we are at currently. That could be applied to a
12 patient's own cells, such that we could remove cells
13 from a patient and alter them in some fashion to
14 produce the cell types that we want, and then
15 transplant them.
16 Or ultimately I feel that what we are
17 going to be able to do from the information that we
18 are going to learn on stem cells is that we will be
19 able to work in vitro with patient cells to get them
20 to perform in a manner that we want without taking
21 them out and putting them in culture.
22 This, I believe, is the future. The
23 scientific challenges to attain our goal of producing
24 safe and effective therapies are formidable. It will
25 take the efforts of many scientists and clinicians, in
1 a variety of disciplines, to bring this endeavor to
3 Now, the stem cells that I am going to
4 talk about today interestingly really do not exist
5 naturally. That is, they don't exist in embryos or
6 fetuses. They are artifacts of culture.
7 But we take tissues from embryos and
8 fetuses and they undergo a type of transformation in
9 culture to provide these stem cells. And this source
10 obviously brings with it a number of ethical concerns.
11 I, as an investigator, who has had to
12 cross this bridge 9 or 10 years ago when I began this
13 work, believe that the ethical issues are manageable.
14 I also believe that it is the
15 responsibility of scientists to candidly and in a
16 timely fashion present the social implications of
17 their research and its technological applications; to
18 provide assessments on reliability, and to participate
19 in the establishment of ethical guidelines and to work
20 within those guidelines.
21 For the past 9 years at Hopkins, we have
22 been in compliance with all institutional, State, and
23 Federal policies in dealing with the cells that we
24 work with.
1 It has not been easy because the landscape
2 has changed in 9 years, and every year there have been
3 new concerns raised, and new issues that had to be
4 addressed, and I think we are keeping up with it.
5 I should tell you also up to this point in
6 time that no Federal monies, no public monies, have
7 gone into our research effort. Now that Federal
8 policy has changed, we do have applications pending
9 before the National Institutes of Health.
10 I also want to point out something that
11 may be surprising to most of you; that in our
12 laboratory at Hopkins that we just are not
13 concentrating on an embryonic or fetal source of stem
15 We are studying stem cells from adult
16 sources, umbilical sources, et cetera. This is the
17 only way that we feel that you can have a scientific
18 advance, and that is to be able to compare and
19 contrast the different sources of stem cells.
20 So side by side, in the laboratory, in
21 experimental paradigms, we are using stem cells from a
22 variety of sources, and this is what I think has to
23 happen to assess which of these sources are going to
24 prove the most effective for any specific type of
1 Another thing that I want to point out to
2 you is that the work on the human cells, I do have the
3 questions that came from your committee in- hand, and
4 many of them are asking what is the status of certain
5 types of work.
6 I just want to point out that this work
7 has been ongoing for a period of 2-to-2-1/2 years, and
8 although we feel that we are making progress, we
9 certainly are going to come up with, well, I don't
10 know as answer to some of your questions.
11 I just want to let you know that we don't
12 have all the answers to this, and we are very, very
13 early in all studies of stem cells, be they from the
14 embryonic or adult sources.
15 I would tell you though that to date the
16 work in our lab and others on embryonic stem cells and
17 the results of that work is certainly consistent with
18 the idea that this is going to prove to be a
19 productive line of research.
20 Well, it is interesting that very few
21 people know you and what you are about, and I think it
22 is important to point out something. My interests, or
23 my research interests for decades, have been in the
24 area of developmental genetics and development
1 I have been labeled as a human
2 embryologist, and my interests certainly are in the
3 area of how an embryo goes from a single cell to a
4 multi-cellular integrated organism.
5 And this is where our research has been in
6 the past 25 years, and I have carried this a step
7 further. We are very interested in congenital
8 malformations and birth defects.
9 I have had a program project through the
10 NIH for many, many years dealing with Down's Syndrome,
11 and we are very interested in trying to determine what
12 the mechanism is that underlies many of the unusual
13 anatomical neurobiological consequences of this extra
14 chromosome in human beings.
15 And this is essentially how I got into
16 this work. We wanted to have in the laboratory a
17 source of cells in addition that we could study at the
18 site or level of the impact of these extra genes.
19 And this obviously is a goal, along with a
20 number of other genetic-based diseases and
21 malformations in the human being. So this is what led
22 to our getting into this area of research.
23 Now, I have to say up front that we are
24 now required by our university to reveal where our
25 monies come from, and these are the sponsors of our
1 research, and there is one sitting in the middle there
2 that I also have to show to you that I am conflicted.
3 And which means that to the sponsorship of
4 this private company, we have received money for
5 research, for which licenses have been negotiated
6 between Hopkins and Geron, and that I am a
7 stockholder, albeit a few hundred shares of something
8 that is trading now at -- and I hate to think about
10 It is not in our possession as you know.
11 It is held in escrow. But nonetheless we do have this
12 arrangement with this company. So I would tell you
13 that this is not the motivation, this connection.
14 Without the sponsorship of this research,
15 this work would not have gone forward over the past
16 seven years. We are not in this business as
17 individuals to make money.
18 Well, having said all of that, let's talk
19 about stem cells. The first thing I want to give you
20 is a little bit of a primer on stem cells so that we
21 are talking the same language, and you have an
22 understanding of where I am coming from.
23 Well, what is a stem cell, and basically a
24 stem cell is a cell that has two properties. It has a
25 property in that it has a capacity for self-renewal,
1 which means that the cell can divide and produce more
2 cells like itself.
3 And it has some type or some degree of
4 differentiative capability, which means that it can go
5 on to specialize into a single cell type, or it can
6 specialize into a number of cell types.
7 And in a developmental sense, if we over
8 time at what our research has told us about stem
9 cells, they fall into a number of categories. Early
10 on in developmental practices, we have a cell that is
12 It can renew, and it can form virtually
13 every cell type that is present in an embryo. As
14 development proceeds, its developmental capabilities
15 become more restricted until we get into different
16 lineages, specific lineages, and its ability to divide
17 also becomes more diminished over time.
18 This has been the classical picture of
19 development. Now, what has happened over the past
20 couple of years interestingly is we find that these
21 restrictions in developmental capability are much more
22 plastic than we had thought.
23 So out here where we thought that these
24 cells are highly restricted, perhaps they aren't so,
25 and when you remove them from the organism and culture
1 them, they have capabilities of forming other cell
2 types, and Catherine will be talking to you about some
3 of these issues.
4 Well, we are going to be talking about
5 embryonic stem cells, and what is it about them.
6 Well, interestingly, we know that these cells are
7 capable of producing virtually every cell type that is
8 present in an embryo, a fetus, or an adult, except
10 And that one happens to be the trophoblast
11 cell, which I will tell you about in a moment. So we
12 consider these cells to be totipotent.
13 They don't have the ability in and of
14 themselves to form an embryo or an individual, okay?
15 They have this other property of self-renewal, which
16 basically with respect to embryonic stem cells means
17 that they will expand indefinitely, and grow
18 indefinitely, and this is a very important property.
19 It means that within the laboratory from a
20 very few cells that you could grow a roomful of these
21 cells very easily. But there is an issue here that we
22 don't know much about, and that is obviously there is
23 a finite probability that at every cell division that
24 a genetic mutation will appear.
1 And there was a paper published recently
2 that indicated that indeed this is the case, and the
3 types of mutation, although the mutation frequency and
4 the mutation rate is greatly -- by several folds lower
5 than in normal somatic cells, mutations do occur in
6 these cells, and they are of the nature of making
7 these cells susceptible to formation of tumors.
8 The uniparental disomy appears and it is a
9 condition about which we should be concerned. And up
10 until this point, in the mouse where these cells were
11 first isolated, and for that work the person who did
12 this, Martin Evans, was awarded the Lasker Award last
14 We know that these lines forming whole
15 animals, which is what they have been used for up to
16 this point, in genetic mutations is getting
17 genetically defined strains of mice.
18 That there comes a time when these cells
19 are no longer productive in doing this and that they
20 lose some quality. So we know that there is going to
21 be a half-life to the use of these cell lines for
22 whatever reason.
23 I just want to point that out, although
24 they do have this replicative ability. Well, where do
25 these totipotent cells come from, and two major
1 sources. The first is this pre-implantation stage
2 which we are going to talk about, and the second are
3 from specific cells within the fetus.
4 I also have on this slide, and by the way,
5 I have given you two handouts. One is the slides in
6 the presentation, and another in a fairly recent
7 Nature review of this material, that you can refer to.
8 I want to point out another source of a
9 cell that is very similar to these two that we have
10 isolated, and that comes as a stem cell for a specific
11 type of tumor called in the old days teratocarcinoma,
12 and now called mixed cell carcinomas.
13 These stem cells, referred to as embryonal
14 carcinoma cells, were first isolated back in the 1970s
15 when I worked on this, and we thought that these would
16 be the answer to finding cells that would produce a
17 variety of cell types that we could work with within
18 the human.
19 And I should tell you that at this point
20 in time that there is a clinical trial going on at the
21 University of Pittsburgh using embryonal carcinoma
22 cells that have been selected for a neural lineage,
23 and so that in culture you can derive neural cells and
24 that these have been placed in the brains of 12 stroke
1 It is a cell that is very, very similar to
2 the two that I am going to talk about. Well, the
3 first source that you are aware of comes from these
4 structures here, which are pre-implantation stage
5 human embryos, and I am sure you are familiar with
7 And where that structure consists of two
8 groups of cells; this outer layer called
9 trophectoderm, and an ectopically placed inner group
10 of cells called the inner-cell mass. It is from this
11 group of cells here that the embryo proper is derived,
12 and it is connected ultimately to this outer layer,
13 which develops in the placental tissue by connecting
14 stock in an umbilical cord.
15 These cells may number only 15 or 20 in an
16 embryo that may consist of perhaps several hundred
17 cells. And in work in the mouse, and subsequently
18 done in humans, first by Jamie Thomson, was that these
19 cells were isolated, placed in a culture condition,
20 which then permits their growth and their conversion
21 into an embryonic stem cell.
22 This process of conversion can be highly
23 inefficient, meaning that you would need a large
24 number of blastocyst and inner cell mass cells to
25 derive a few cell lines.
1 In some people's hands, it can be more
2 efficient, but there is an issue with that. A second
3 source of cells with the same features was identified
4 in the early 1990s, first by Peter Donovan at NCI.
5 And what they were attempting to do were
6 to culture long term cells that are called primordial
7 germ cells. These are diploid cells that are present
8 in an early embryo that eventually give rise to egg
9 and sperm.
10 And they isolated, and this is
11 superimposed upon a human fetus, they isolated from
12 the gonads, the gonadal ridges, these large cells,
13 which at the time of isolation in humans are about
14 20,000 of them present in a gonad, and placed them in
15 culture and essentially ended up with the same type of
17 This is what a human EG culture looks
18 like, this clustering of cells and I want to point out
19 that there are cells in the background here which are
20 the so-called feeder layers.
21 All of these cell lines are derived on
22 feeder layers, and all the lines that were approved by
23 Mr. Bush, and all the lines that we have, are derived
24 on a mouse feeder layer, and this is a point of
25 contention, meaning that we are concerned now about
1 the fact of any endogenous viruses being transferred
2 from other animal tissues into the human cells.
3 And the FDA must deal with this at this
4 point in time, but we do not have permission on the
5 use of Federal funds to derive new lines, avoiding
6 this issue of other animal products.
7 But they are grown on feeder layers. They
8 are established and grown on feeder layers of other
9 species. If we compare different properties of these
10 cell types, and I bring this up -- some of these are
11 of no value to you immediately, but these are the
12 criteria that one must use to say whether or not you
13 have a cell line.
14 It is very important, and of the 80 some
15 lines that are now purported to be available, I can
16 guarantee you in talking to many investigators from
17 around the world that only a handful of these are bona
18 fide cell lines, and/or available to investigators.
19 Now, this may beg the point and that that
20 may be enough to serve the purposes in the immediate
21 future. But really the majority, the vast majority of
22 so-called lines available do not meet the criteria
23 that are now used to say whether a line is a line.
24 Now, how do we -- we are very interested
25 then in two things here. One is the basic science
1 aspect of this, and of course what is driving all of
2 this is the hope for some type of transplantation
4 Let's talk a minute about the basic
5 science. What we have in the laboratory now are
6 cultures of cells in the plate that can form any cell
7 type in a human body.
8 Now, the argument is have we demonstrated
9 that you can get out of these all 200 and some cell
10 types? No. You only find what you are looking for.
11 What we have found though are a large
12 number of cell types that are present in the human
13 body within these dishes. The problem at the moment
14 is getting homogenous population of pancreatic islet
15 cells or blood cells, or muscle cells.
16 This is the real part of the scientific
17 struggle here, and coming up with the paradigms to say
18 can we take a cell that can form any cell type, and
19 get it to form but one cell type.
20 And to do this we have to rely upon our
21 knowledge coming out of molecular embryology as to the
22 genetics and what not involved in any type of cell
24 And this is really the limiting issue at
25 this point in time, getting these purified populations
1 of cells on demand. There are strategies that are
2 used that we do pretty good at, and we will take the
3 initial populations of cells, and we can change feeder
4 layers, and we can change growth factors, and we can
5 put them in different types of cultures and force them
6 then to begin to specialize.
7 But they are mixed cultures, and within
8 the same dish you are going to find neurons and
9 muscle, et cetera. And we must then go another step
10 and begin to sort out either through procedures called
11 flow sorting based on what is on cell surfaces to get
12 then pure populations of hematopoietic stem cells,
13 muscle cells, or neuro cells.
14 And this works fairly well. We can get
15 cultures of dopanergic neurons that are 80 percent
16 pure, and we can get cardiac muscle that is 97 percent
17 pure, et cetera.
18 But we are a long way from isolating in a
19 homogeneous fashion the various types of cells that we
20 would like to get. Some of them were doing well at
21 and others were not.
22 And it is going to require an extensive
23 amount of research to achieve this. Now in going to
24 transplantation therapy -- we are going to jump a
1 little bit ahead here, and if we start, this could be
3 If we start with this population, we do
4 not transplant into anybody, or into an animal at this
5 point, one of the stem cells. You don't do it. The
6 reason that you don't do it is this.
7 These stem cells are capable of forming a
8 variety of tissues, and they will form tumors, and
9 these tumors are these mixed germ cell tumors that
10 contain a variety of cell types.
11 They are called teratomas in the old
12 literature. Monster. I mean, they are contained in a
13 mixed array, and you can see teeth, sebaceous glands,
14 hair, bone, parts of the gut, et cetera.
15 So what you have to do to make this work
16 is you want to at least get cells that you have
17 treated somehow in a dish into some of these more
18 defined lineages that are away from this capacity to
19 form tumors.
20 So that we then begin to select tissues
21 downstream, all right? Part of the problem, and you
22 will read this in the literature, is how good your
23 selection is, is also indicated by whether or not when
24 you take myocardiocytes that you say, oh, these are
25 all 100 percent myocardiocytes, you transplant them
1 into the wall of the heart, and you end up with a
3 This happens, and we are into the central
4 nervous system, and you end up with a teratoma within
5 the brain. So getting rid of those initial stem cells
6 are essential, and we have ways of doing this
7 genetically, but I just want to point out that this is
8 an issue.
9 To say nothing about the fact that we do
10 not know whether any cell downstream here has the
11 capacity to revert. We know very little about that at
12 this point in time.
13 So let me give you an example. There are
14 many of these coming out in a number of laboratories,
15 most of them in the mouse in which lines have been
16 derived in different lineages, and they have been
17 transplanted into animals to show proof of concept,
18 and that you can isolate a specific cell type, and you
19 can transplant it, and it will function within the
21 I would like to give you now an example
22 from our work at Hopkins. It is an unpublished work,
23 and it is now under review, but I think it is
24 important because it really illustrates several points
25 that are critical here.
1 We have taken our human cells and grown
2 them under culture conditions that would select for
3 specific types of lineages, and whether it is neural,
4 or whether it is muscle, et cetera. And now we have,
5 I believe, in our laboratory over a hundred a hundred
6 lines like this, of the human lines.
7 And in the one example that I want to
8 present to you, which was done with members of our
9 department of neurology, and in collaboration with our
10 lab, is a model, using these cells in an animal model
11 of the motor neuron disease.
12 And in this study, these animals are
13 treated with a virus that destroys lower motor
14 neutrons, so that animals become paralyzed, and they
15 are paralyzed because they lose the big nerve muscles
16 that in your spinal cord hook your muscles up to the
17 central nervous system.
18 So that in a period of 10 days following
19 the injection of the virus into the brain, the animals
20 become paralyzed, and we have gone to great lengths to
21 show that it is really the ventral roots that are
23 You wipe out these neurons and these
24 animals never recover. They never recover. So what
25 we have done is to take our human neural cells out of
1 this and infuse it into the spinal cords of these
2 rats, and to look then for the recovery of motor
4 This is a rat out for a mid-morning
5 stroll, and this animal is infected with the virus,
6 and it is a virus that really leads to an
7 encephalomyelitis, and within a period of 10 days the
8 animal is paralyzed.
9 We can document exactly what this
10 paralysis is about. The virus is cleared, and shortly
11 thereafter we will put a cannula into the lumbar
12 region of the animal, and infuse 300,000 cells into
13 the cerebrospinal fluid, and these cells will float
14 all the way up to the hind-brain.
15 And then we monitor the motor activity of
16 these animals, and within a period of a few months, we
17 begin to see animals that can now place their limbs
18 underneath them, and that can draw them up, support
19 some weight, and begin to push off.
20 And at the high end, within a several
21 month period, we can have animals that are now
22 walking. And the issue is why are they walking. And
23 what we have learned, although it is not as you can
24 see a normal gait, et cetera, and we have really
25 documented this as well, they are walking.
1 And why are they walking? Well, initially
2 what we felt was this. This is a panel showing cells
3 within the ventral horn of those animals and I want
4 you to look at this cell here.
5 This cell, based on its marker, and based
6 on its physical characteristics, and molecular
7 characteristics, is a human motor neutron cell that
8 has been specialized out of these neural precursor
9 cells, that has sent an axon out into the periphery at
10 least two centimeters.
11 And we have been able to cut the sciatic
12 nerve out on the limb of this animal, place a dye at
13 that site, and that dye is picked up by that axon, and
14 brought back to the cell body that extended the axon.
15 And it comes back, and this is the green
16 stuff here, and it comes back then into the cell body
17 of the human motor neuron. We have gone on to
18 document how many human cells are present, and what
19 they are as far as the phenotype is concerned, to see
20 -- you know, yes, they are forming glia, and they are
21 forming a variety of cell types within the ventral
22 horn of that animal.
23 Interestingly, and one of the safety
24 issues that we find is that 50 percent of the cells
1 don't do anything. And we are a little bit concerned
2 about that.
3 I mean, is it good to have all these cells
4 in there that aren't doing anything, but this is an
5 issue that we have got to resolve. Well, it turns out
6 that this is only part of the answer. It turns out
7 that the human cells at the same time are producing
8 growth factors that rescue and enhance the
9 regeneration of the animal's own cells within the
10 ventral horn.
11 And so this has led us then to set up
12 experiments to try to figure or try to determine what
13 growth factors it is that is causing the growth of
14 axons in those mice and in rats in the ventral horn,
15 and it may be that eventually we can use just the
16 combination of those growth factors to elicit this
17 response. We don't know.
18 So these cells are serving in a dual
19 capacity, which is somewhat exciting. We have taken
20 the human cells and we now have grafted them into
21 monkeys. They were in monkeys for over a year.
22 This was a safety study to in fact show
23 that we are not getting tumors formed. I think you
24 can appreciate one of the major issues here that we
25 are going to be faced with, with this type of
1 approach, is animal experiments are of a very short
2 duration. Mice and rats are for periods of several
4 Monkeys we can go much longer. How much
5 data is going to be needed to convince the FDA that
6 this is a safe approach, and this is something that is
7 being debated now within the FDA and it is a difficult
9 But here we show human cells, and that is
10 these blue ones that have been in this monkey, and in
11 this case for 180 days, but we are now out a year, and
12 we can show that these cells are forming specialized
13 structures and they are non-tumorigenic.
14 The next phase is to look at a graph model here that
15 is functional.
16 DR. KASS: Can I just ask a question?
17 DR. GEARHART: Sure.
18 DR. KASS: What has been injected here?
19 DR. GEARHART: Oh, I'm sorry. These are
20 the same -- what has been injected into this monkey
21 are the same cells that were injected into the rat.
22 The same cells. They were human cells --
23 DR. KASS: Neural precursors?
24 DR. GEARHART: Neural precursor cells.
25 The same cells, the same culture cells. A major issue
1 that we must discuss and that we are concerned about
2 is graft rejection. Obviously, anything that you grow
3 up, unless it matches the patient, is going to be
4 subjected to that, and now we get into an area which
5 Dr. Kass has mentioned earlier.
6 But what are our options here? What are
7 the options of being able to grow these cells into any
8 of these lineages and then to transplant them and not
9 have rejection?
10 Well, there is a long list, and it starts
11 with, well, maybe what we ought to do is derive
12 hundreds of ES and EG cell lines, and then you would
13 have a best match for a patient. Not very practical.
14 Can we use the patients own cells, and you
15 will hear about some of this shortly. Should we use
16 immunosuppressive therapies. We would like to get
17 away from that.
18 Can we use what the tissue engineers are
19 referring to as sequestering grafts, and what this is,
20 is you can take grafted cells and put around them
21 matrices that will not permit other cells to touch
22 them, but yet they can produce products, or they can
23 function in a graft.
1 So you are trying to hide them from the
2 host immune cells. How effective that is going to be,
3 we don't know.
4 Can we perhaps come in and genetically
5 modify, which is easy to do in these cells with the
6 histo-compatibility genes, so we can make them more
7 like a patient that is going to receive these cells.
8 Or is it possible that we may end up being
9 able to produce cells that may be universal donors.
10 Again, we are trying this, and at the moment it is
12 Clearly the one thing that has worked is
13 the issue of nuclear transfer therapy, the so-called
14 therapeutic cloning, in which as you know the argument
15 is to take a cell from a patient, and fuse it to an
16 enucleated egg, derive a blastocyst, recover the inner
17 cell mass, culture it out, and then these embryonic
18 stem cells would match the genome of the patient.
19 Is this a pipe dream? The answer is no,
20 and I will give you an example of that in a moment.
21 To get around some of the issues with the human
22 cloning, embryonic cloning in humans, you have seen
23 reports in the Wall Street Journal and other places
24 which I can confirm are real, in which there are
25 attempts now to take human cells, human nuclei, place
1 them for example into rabbit eggs, enucleated rabbit
2 eggs, and grow up a blastocyst, and generate stem
3 cells that have human nuclei and rabbit mitochondria.
4 And the argument has been made here that,
5 well, these cells would be perfectly fine for an
6 autograft, and this isn't accurate. We know that
7 mitochondria produced polypeptides that are integrated
8 into the cell membrane, and are actually considered to
9 be minor histocompatibility antigens, and will be
10 recognized and rejected by the host from which the
11 nucleus came from.
12 So this really is not getting around the
13 issue of the graft stuff at all using other animals,
14 and we are a little bit concerned about how this is
15 being handled.
16 So, let me give you an example, and one
17 which you should read these papers if you haven't from
18 Rudy Jaenisch and George Daley at MIT, using the
19 nuclear transfer therapy, or the therapeutic cloning,
20 to do two things.
21 What they did was to take a mouse that had
22 a genetic mutation in genes that are important as far
23 as the immune response is concerned. And they took
24 cells from this mouse, took the nucleus out of the
1 cell, and placed that nucleus into an enucleated egg
2 to produce a blastocyst from a cloned embryo.
3 They took the inner-cell mass cells out of
4 that, and generated embryonic stem cells, that then
5 are the same genome type as this animal, and then went
6 in and repaired genetically the mutation within those
8 And then differentiated these cells into
9 the hematopoietic stem cell component, transferred
10 them back into this animal that had the mutation, and
11 the transplant took, completing the whole
12 hematopoietic system, and in rescuing that animal.
13 So this is a proof of concept kind of
14 experiment, and I urge you to read it. It is an
15 extremely powerful illustration, not only of the
16 therapeutic cloning end of things, but also the
17 ability then to come along and correct the genetic
18 mutation and the reference was given to you.
19 Another argument has been made that we
20 should be using perhaps just eggs that have been
21 stimulated to form embryos, and these are parthenotes.
22 And the argument here has been that we can
23 then use these directly into the female from which the
24 eggs were taken. I just want to point out that in my
25 opinion that this is going to have very low usage.
1 You are going to have to recover embryos
2 or eggs from patients, post-pubertal, and pre-
3 menopause. The window is going to be fairly short, I
4 think, for many of the therapies that you would want
5 to effect.
6 And the other issue is that we don't know
7 much about cells that are derived this way, and how
8 viable, and how functional they are going to be. But
9 this has been used or promoted also as a source, and
10 this is an illustration of where you take those cells.
11 All of this type of technology, I just
12 want to let you know, and I know that you are
13 grappling with this, but even within the field of the
14 scientists are beginning to argue about what is an
15 embryo and what isn't an embryo.
16 So any arguments that you have within your
17 council on this, I will tell you is also being held
18 among biologists. I think that my own personal
19 feeling is that anything that you construct at this
20 point in time that has the properties of those
21 structures to me is an embryo, and we should not be
22 changing vocabulary at this point in time. It doesn't
23 change some of the ethical issues involved.
24 What are some of the problems here, and I
25 will summarize this a little bit. Current research.
1 Well, we have to come up with better ways of having
2 high efficiency differentiation protocols resulting in
3 homogeneous cell populations.
4 We are dealing with growth environments,
5 and genetic manipulations, and we are trying to define
6 stages of cell differentiation within our cultures.
7 And assessing whether or not the
8 differentiated cells that we are getting out are
9 normal and completely functional. And this is in a
11 And let me tell you that there are
12 examples of where you can spend all of an effort
13 studying something in a dish, only to find that if you
14 pop it in an animal that it doesn't behave how you
15 think it is going to behave. We have a lot to learn
17 I think you can imagine that what is going
18 on in a dish is not exactly what is going on in a site
19 where you transplant. The whole issue of grafting,
20 and how you put it in, and the safety issues, and that
21 cells migrate away, and they differentiate, and will
22 they form tumors, and then the issue of the immune
24 These are all, you know, formidable
25 obstacles that lie ahead. I mentioned to you that we
1 can use cells individually, and have been used in a
2 variety of paradigms in our collaborators of single
3 cells, and the tissue engineers are now taking these
4 different cell types and seeing if they can
5 reconstruct or construct organal aids or tissues to do
6 in-grafting, and thee has been some success with this
7 at this point.
8 Finally, to me, the future is going to be
9 that the basic science coming out of this is the most
10 important element, and that from that information we
11 are going to be able, I think, to take patient cells,
12 where appropriate, and I say where appropriate because
13 if you have autoimmune disease, or in cases where you
14 have an injury, spinal cord injury, or stroke, or
15 heart attack, and you don't have time to take that
16 patient's cells, you are going to have to come up with
17 different paradigms.
18 But I think we are going to be able to
19 eventually coax a patient's own cells to behave in a
20 manner that we want to, but we are going to learn this
21 I think through the study of stem cells.
22 The last thing I will say is I know that
23 you want to ask, well, what is the future going to
24 bring, and I am concerned about predicting the future.
1 I can't even do this on a three year NIH grant and
2 this is what is expected of us.
3 You know, what is going to happen here. I
4 certainly think that everything that has happened up
5 to this point is consistent with success in this area,
6 and I could get into more predictions in a moment.
7 But we are always asked when is this going
8 to happen, and it is going to be I think based on
9 specific cell types, and on, and on, and on. But the
10 predictive thing is very, very difficult.
11 Well, I thank you for your attention, and
12 I hope that this was enough of a primer to add more
13 meat to your discussions. Thank you.
14 DR. KASS: Thank you very much.
16 DR. KASS: We were only physically in the
17 dark, but we are grateful for your enlightenment, Dr.
18 Gearhart, and the floor is open for questions, and
19 comment, and discussion. Don't forget that you have
20 to turn your microphones on to be heard. Jim, go
22 PROFESSOR WILSON: Dr. Gearhart, do you
23 foresee that it will ever make a difference whether
24 cells that are transferred for human cell regeneration
1 come from cloned eggs, or from the retrieval from IVF
2 eggs? Does it make a difference what the source is?
3 DR. GEARHART: Well, I think in the short
4 term that it will. I think the only way we have
5 around the immune rejection story at this point is
6 from cloned embryos.
7 For a patient in which you can predict
8 ahead of time is going to need stem cell therapy and
9 you have the time and money available to do the cloned
11 I would like to think that this is going
12 to be a transitionary period, and that we will not
13 have to rely upon this in the long term, and that we
14 will be able to take for any specific disease a stem
15 cell, or a derivative of a stem cell that may come
16 from the adult source, the umbilical source, the fetal
17 source, or embryonic source.
18 I mean, whichever presents, and that we
19 will have ways of dealing with this graft rejection
20 story other than through the cloning of human embryos.
21 PROFESSOR WILSON: If I could just
22 supplement my question with a related one to which you
23 referred. What is your current assessment of the
24 value of adult stem cells, as opposed to embryonic
25 ones, as a source of organ regeneration currently?
1 DR. GEARHART: Oh, I think it is a very
2 viable option and I think NIH should fund it. I think
3 that from what we see in the work, and Catherine will
4 present a nice overview of this, that this is going to
5 be a good source of stem cells.
6 They have some issues that they have to
7 overcome, issues of expandability, and plasticity,
8 that we feel are -- that have not been demonstrated as
9 well as embryonic stem cells, but I think that
10 eventually we will be able to overcome this.
11 But I think part of the knowledge of
12 overcoming it is going to be coming from our studies
13 of cells that have those capabilities, and being able
14 to transfer that information to those other cells.
15 So I think we are going to come up with --
16 I believe that in the stem cells, cell-based
17 therapies, that we are going to identify certain adult
18 sources that are going to be good for some diseases,
19 some injuries, and embryonic sources for others.
20 So I think we are going to mutually
21 proceed on this and benefit from it.
22 DR. KASS: Please, Elizabeth.
23 PROFESSOR BLACKBURN: Dr. Gearhart, you
24 can give us I think a unique perspective on the
1 comparison between adult, and embryonic, and fetal
2 stem cells.
3 And in particular many of us read the
4 recent papers, the scientific peer-reviewed papers
5 that came out with respect to the adult stem cells,
6 and the interpretation of their plasticity being cast
7 in some considerable doubt by the observation that
8 there was cellular fusion of those cells which had led
9 to in these particular cases examined a mistake in
10 interpretation of their plasticity.
11 And I wondered if you could give us your
12 perspective on that aspect, which extends Jim's
13 question somewhat.
14 DR. GEARHART: I will do so in the face of
15 Catherine sitting back here, who is --
16 PROFESSOR BLACKBURN: Yes, I am going to
17 ask her, of course, about this, too.
18 DR. GEARHART: -- actually done those
19 experiments. Clearly the most difficult experiments
20 that we have had to address and interpret are those
21 utilizing adult stem cells that have been placed into
22 the blastocyst of mice to create chimeras.
23 And in those chimeras, we see that the
24 descendants of those adult cells gave rise to many,
1 many lineages within the embryo, and this was really
2 the issue. How did we explain this.
3 And from the studies of Austin Smith and
4 others that you are referring to, the implication was
5 that when those cells were transplanted into that
6 blastocyst to generate the chimeras, that a subset of
7 these cells fused with the hosts own cells and it was
8 those fusion products then that gave rise to the
9 variety of lineages.
10 At the moment that is an implication, and
11 that has not been demonstrated in the embryo. It has
12 been demonstrated in the dish that they had that
14 So we are now waiting and putting pressure
15 on Catherine, and Freizen, and others to look into
16 those animals to see if they can recover those
17 specialized cells that were derived from or that had
18 the adult phenotype if you know what I mean, the
19 marker, to say are you truly of the adult stem cell
20 lineage, or do you have other markers present, other
21 chromosomes present, that come from host cells.
22 So until we see that data -- you know, I
23 will wait. That is something that can be looked at
24 scientifically, and that is as far as I would go with
25 you, Elizabeth, at this point.
1 It is an interesting observation, and we
2 will see if it actually is the answer.
3 PROFESSOR BLACKBURN: And just to extend
4 on what you said, I think what it does now do is to
5 demand that the onus be put on the researcher to show
6 that there has been a plasticity or
7 transdifferentiation, and there are other set of
8 criteria, which would be karyotype and multiple micro-
9 satellite, polymorphisms -- sorry to get overly
10 technical -- and other genetic markers.
11 There are clearly tools in hand, and so it
12 seems as if every experiment can in fact be subjected
13 to those sets of analyses now.
14 DR. GEARHART: Right.
15 PROFESSOR BLACKBURN: And will need to be
16 before we can get a good view of this.
17 DR. GEARHART: Right.
18 DR. KASS: Rebecca.
19 PROFESSOR DRESSER: I have four questions,
20 and maybe if I say them all it will be possible to
21 answer some of them together. One, I was wondering if
22 the rats are being given immunosuppressants in this
24 And then you said a problem with the
25 rabbit eggs is that the mitochondrial DNA might cause
1 rejection, and so I wondered if that would happen with
2 a cloned human embryo as well if the egg came from
3 another person, and if you are trying to do a therapy
4 that is compatible with a patient.
5 And let's see. The feeder layers, I was
6 wondering if they have available feeder layers that do
7 not come from animals or what the state of that
8 development is.
9 And then finally what about the fact that
10 if you are creating a blastocyst from a patient's
11 cell, and if the patient, let's say, has cancer or
12 some condition that could be related to genetics,
13 would the stem cells somehow perhaps be risky?
14 DR. GEARHART: There is no question in my
15 mind that the possibility exists that if you are doing
16 an egg donor, and nuclear transfer into an egg, that
17 there possibly exists that that cell -- that the
18 embryonic stem cells derived from that could be
19 rejected. Absolutely.
20 Now, how do you test this? I mean, where
21 do you test it. This almost comes under the same
22 criteria that I have for anyone coming to -- if I was
23 on an IRB and they wanted to clone a human
24 reproductivity, what data do you present before you
25 permit it to go.
1 To me, it is one of these things where you
2 need perfection before experimentation, or without
3 experimentation, which is something in science is
5 PROFESSOR DRESSER: Well, you could test
6 that in an animal, right? I mean, you could at least
7 see --
8 DR. GEARHART: Well, you can, and we could
9 set it up in an animal, but the issue is -- I mean,
10 where you are very defined and to demonstrate it by
11 doing it into a different strain of mouse. There is
12 no question about it.
13 But whether or not that would carry over
14 in polymorphisms that exist in human, again you are
15 still faced with human versus rodent.
16 The feeder layer issue. It is one that is
17 being taken on, and there is no banning of this type
18 of work with private money, and clearly there are a
19 number of investigators, laboratories, working on
20 establishing feeder layers from human tissue that
21 could be used, and I think that this is very
23 So those studies are certainly under way.
24 We have used a variety of different human tissues as
1 well to look at in our studies. Oh, the very first
2 question that you asked. I'm sorry, it was again?
3 PROFESSOR DRESSER: For the rats --
4 DR. GEARHART: Oh, sorry. We did animals
5 that were immunosuppressed and animals that were not
6 immunosuppressed. And we did not find a great deal of
7 difference in the short term, although -- I mean, as
8 far as any type of destruction of cells and things
9 like that, although clearly in the animals that were
10 not immunosuppressed that you could see reactive cells
12 So clearly in the monkeys
13 immunosuppressed, absolutely, and so we have done them
14 both. And then the blastocyst question?
15 PROFESSOR DRESSER: If it comes from a
16 patient with a particular disease.
17 DR. GEARHART: Yes. Clearly where there
18 is a genetic basis of any type of a disease, you would
19 be concerned about reintroducing the same cells that
20 were subjected to whatever the disease process was.
21 And I think that this carries over also
22 into, for example, the diabetes work, where if you
23 have an attack on insulin itself, you know, is this
24 going to be a viable alternative, and there are some
25 evidence now that you can alter the insulin molecule
1 to make it not recognized by some of the autoimmune
3 I should say that there are a number of
4 laboratories -- and this is one area that is being
5 emphasized in the use of human cells, including our
6 own, with Mike Shamblott, where we have lines that are
7 -- human lines that are insulin producing that you can
8 pop them into animals, and demonstrate that they can
9 produce human insulin.
10 And we are very encouraged by some of
11 these early results. But I would still contend that
12 we have a long way to go to carry that into some type
13 of clinical application. We have a lot of questions
14 to answer.
15 DR. KASS: Janet.
16 DR. ROWLEY: Well, I, too, have multiple
17 questions and I want to thank you for a very lucid
18 presentation. That helps a great deal. I would like
19 to first -- and I think I will do these one at a time.
20 It is a substantial question as to what
21 value the embryos that are left over from IVF can play
22 in this whole process as compared with embryos that
23 you develop for either a particular purpose, or just
24 straight off.
1 And my understanding was that maybe some
2 of the embryos were sufficiently mature so that maybe
3 the cells derived from IVF would not be useful in
4 developing, say, cells lines or things. And I would
5 like your comments.
6 DR. GEARHART: One of my hats at Hopkins
7 when I moved there in the late '70s was to develop the
8 IVF program. So we are very well tuned into the
9 issues of IVF, and clearly in an IVF procedure the
10 best embryos obtained are those that are used first in
11 first transfers.
12 So that generally those that are left over
13 are of the ones -- we don't want to call it a lesser
14 quality, but at least as far as our eye is concerned,
15 and how we judge grades of embryos, based mainly on
16 morphology to be honest, and more currently we are
17 looking at biochemical parameters that we can measure
18 in the media in which these cells are growing that
19 something has been secreted to have some kind of a
21 And that clearly those that are the spare
22 embryos generally are those of -- let's say, what we
23 deem, and knowing what that means, of lesser quality.
24 So what does that mean? In most cases,
25 they have not developed far enough along, which means
1 that if they are left over that you take them back out
2 of the freezer, and you try in your culture conditions
3 to get them up to this blastocyst point.
4 If you can't get them to a blastocyst
5 stage, you can't derive the cells. If there is no
6 inner cell mass, you can't do it. And you find that
7 you are compromised there, and that generally these
8 are not very good embryos.
9 So one could argue that overall that you
10 would expect to have a low efficiency yield with
11 respect to taking in embryo and deriving a line from
12 spare embryos in an IVF program. That is in general.
13 DR. ROWLEY: Okay. You mentioned
14 modifying the histocompatibility locus, and I would
15 have thought that there is still so much that we don't
16 know about the MAC that that would -- I mean,
17 obviously anything can be done in the future with
18 time, but do you look on this as practical?
19 DR. GEARHART: Well, back in the ancient
20 days, in the early '80s it seems in this field, Oliver
21 Smithies and others did do knockouts of Class I and
22 Class II genes, in an effort to determine whether or
23 not this could prolong grafts into animals without
1 And that depending on the tissue or the
2 organ, there was evidence that this indeed could be
3 the case, and not that it was an indeterminate thing,
4 but just by days, or weeks, or months, that this was
5 the case.
6 What they didn't know about at that time
7 were NK killer cells, and those kinds of things, and
8 the importance of other determinants which must be on
9 cells. They wiped everything out.
10 So some labs are now taking a look at this
11 to see if it is possible then to rebuild back some of
12 these markets. But it is a matter of speculation at
13 this point whether or not this could occur.
14 Now, what we can talk about I think is it
15 possible to take using the act of transgenesis and
16 things like this, where we could move big pieces of
17 DNA; of taking part of a patient's chromosome-6, you
18 know, and cloning that into a stem cell after knocking
19 out some of it, and we may get some degree closer.
20 But that says nothing about the myriad of
21 other loci that could be involved as minor
22 histocompatibility problems. So, some of it is
23 speculation, but I think it is also testable at this
24 point in time.
1 DR. ROWLEY: And my last question is
2 coming back to the 80 plus cell lines, and you raised
3 concerns, which many of us have, as to how useful some
4 of those are going to be.
5 DR. GEARHART: Right.
6 DR. ROWLEY: Could you expand a little
7 bit, in terms of whether you think they are really not
8 going to be long term cell lines, and that is your
9 concern, or whether there are other aspects.
10 DR. GEARHART: Well, I have many concerns,
11 and I hope that I can get them all in. I mean, look,
12 we were all thrilled when Mr. Bush made the decision
13 to move forward with this and establish cell lines to
14 permit the work to go forward. There is no question
15 about it.
16 But as we looked into -- and by looking
17 into, it was a practical matter. Many investigators
18 around the world, and I have close contacts with
19 colleagues in Germany, and in France, and in England,
20 and Japan, and Australia, and on and on, as we compare
21 notes all the time on our results of research, as well
22 as on practical things like this, and on political
24 I mean, there is no question that we have
25 to keep abreast, and what happened, particularly from
1 the German investigators, which is significant, as you
2 know, in Germany, they are not permitted to derive
3 cell lines.
4 And for a while they were not permitted to
5 use those that were even derived, and recently their
6 parliament voted to permit the use of existing cell
7 lines as of January 2002.
8 But what happened was that when these
9 investigators set about to import cell lines, and
10 contacted the registry list at the NIH, which
11 continues to grow each day, and more lines are added
12 to it as you know, it turned out that many of the
13 lines were not defined.
14 Someone just reported that they had a
15 clump of cells growing in a dish, and they didn't have
16 any of these parameters or very few of them done.
17 And this reduced the list substantially,
18 quite substantially, down to -- we are talking about,
19 say, a dozen. And then the issue came up as to, well,
20 are these -- can they be imported without a stringent
21 material transfer agreement, and with a reach through
22 clause that would say that anything that you would do
23 with those lines belongs to the person giving you the
1 And this reduced the line substantially.
2 And then other lines are not available because if you
3 needed to get them, you needed NIH funding, and only
4 NIH funding. You could not use private funding with
5 them, and on and on.
6 And so it drastically reduced down the
7 number of lines that are practically available. Now,
8 whether or not this will have a major impact, clearly
9 the NIH is receiving grants, and we have been
10 reviewing grants, and using the existing approved
11 lines, the few that one can get.
12 And the work will go forward, and whether
13 or not that will be sufficient, and we recognize that
14 there is going to be a half-life to these lines for
15 various reasons, and that there will come a time if it
16 proves effective in the basic science part of this to
17 move forward, that we should be looking at being able
18 to generate new lines.
19 And the issue of the feeder cells is a
20 major issue as well, and to begin to establish lines
21 on human cells so that we are not faced with that
22 anything that we derive from this now, and it is
23 important to consider, has to be considered as a
1 Although it is a human line, the FDA
2 requires that if it has seen these other products, it
3 has to be considered a xenograft, which sets up a
4 whole new set of criteria for moving this into the
5 clinical applications.
6 So I think there are reasons why we should
7 eventually be permitted to derive new lines. Well,
8 I'm sorry. We can do it now on private money, but
9 anything that is derived cannot receive Federal money
10 for support.
11 DR. KASS: There are people waiting in
12 line, but can I get a clarification on this question
13 that came up in your answer to Janet about the
14 durability and longevity of the lines, and on the one
15 hand, one says that the embryonic stem cell lines,
16 their great virtue is that they can be self-renewed
18 On the other hand, they have a half-life,
19 perhaps because of accumulated mutations. Could you
20 say a little more? I mean, some people claim these
21 are eternal lines.
22 DR. GEARHART: Right.
23 DR. KASS: And could you say something
24 about the possible differences between human and mouse
1 with respect to renewability, because I think it is an
2 important factor.
3 DR. GEARHART: Well, the issue is maybe
4 they are eternal, but can you still use them. They
5 can still divide indefinitely, but they may not --
6 DR. KASS: But they are no longer the
8 DR. GEARHART: Yes, they are no longer the
9 same, and they may not give you the biologic
10 properties that you need. Strangely enough, Leon,
11 there have been very few publications up to this
12 point, and up to this point there is one that I can
13 cite for you, and I have it in answer to some of your
14 questions by Joe Stanbrook at -- Peter Stanbrook, at
15 the University of Cincinnati, in which he looked --
16 these were mouse lines.
17 And he looked at the frequency and rate of
18 mutation within several mouse lines, and contrasted
19 those with several schematic cell lines that were in
20 the lab as well.
21 And he found that indeed the mutation
22 rates -- and what you do is you pick certain genes to
23 look at changes, and to look at chromosome lost or
1 This paper was published in PNAS in the
2 March 19th issue for those who are interested, and
3 what he found was that the frequency and rates of
4 mutation were orders of magnitude less in the
5 embryonic stem cell line than in the schematic cell
7 And you are looking at a rate of generally
8 10 to the minus 6 frequency within any mammalian cell
9 as it is divided. But what he did find, and that was
10 a bit troublesome, was that the type of mutation that
11 appeared in the embryonic stem cell one led to what is
12 called uniparental disomy, which is a situation where
13 you end up with homozygosity across a region, or
14 across chromosomes or regions of chromosomes, that
15 gets rid of really the dominant tumor suppressor
16 genes, which then raises the issue that these cells
17 may be more susceptible to tumorigenesis than others.
18 Now, that is the only report, and I will
19 tell you that in several laboratories what is being
20 done now with the human lines, and that is using
21 express sequence tags, for example, and you can use
22 10,000 of them, they are looking at mutation rates at
23 10,000 loci, if you know what I mean, over time in
24 culture passage, after passage, after passage.
1 So we will get information on this
2 parameter, and how significant it is going to be, I
3 don't know, but one would predict that clearly there
4 is going to be an accumulation of mutations within
5 these cells.
6 DR. KASS: Okay. Thank you. I have
7 Michael -- well, also, was that on this point?
8 PROFESSOR BLACKBURN: Just a very brief
9 clarification. Did the absolute frequency of
10 uniparental disomy go up? Was it an absolute
11 frequency increase, or simply did it relatively
12 increase as you looked at the whole spectrum of
13 mutations in the mouse embryonic stem cells?
14 Do you see the difference that I am trying
15 to get at?
16 DR. GEARHART: Yes.
17 PROFESSOR BLACKBURN: That if it were an
18 absolute increase, that is a reason for concern, much
19 more than if it were simply a relative increase in a
20 number that has already gone down by --
21 DR. GEARHART: These numbers are rates,
22 and so I believe it is an actual number. In other
23 words, it was a real --
24 PROFESSOR BLACKBURN: An absolute
1 DR. GEARHART: Yes, an absolute increase.
2 PROFESSOR BLACKBURN: So I just wanted to
3 make sure that I understood the numbers here.
4 DR. KASS: Michael Sandel, and then Frank.
5 PROFESSOR SANDEL: I would like to go back
6 to the adult stem cell versus embryonic stem cell
7 question, and ask it in a slightly different, and
8 maybe more pointed, form.
9 As you know, there are some people who
10 regard embryonic stem cell research as morally
11 objectionable. I am not asking you or trying to drag
12 you into that debate. But I would like to know your
13 view on the following scientific question.
14 If adult stem cell research in the best
15 case scenario redeems its promise, what would we lose
16 medically and scientifically if we ban embryonic stem
17 cell research, or imposed a moratorium on it for a
18 period of time, until we could assess what adult stem
19 cell research could achieve?
20 DR. GEARHART: I personally think it would
21 be a tragedy, and for the following reason, if this
22 was to happen. I think the length of time that it is
23 going to take to assess whether the adult stem cell
24 avenue is going to provide the potential therapies
25 that we are thinking about, is going to be years.
1 And I think for us to deny at this point
2 any avenue that has the potential of the embryonic
3 stem cell story is a tragedy to those people who need
4 or who will need these cures.
5 And I think that it is a time element. If
6 this could be done in a year, I would maybe listen to
7 that argument. But it is going to take years to
8 really assess any of these approaches.
9 And I really think they should move
10 forward together. I think we are going to learn in
11 both directions how to utilize information coming out
12 of these studies that would benefit, for example, or
13 enable us to understand more about the adult sources
14 if this is going to be the emphasis, and to really
15 make them effective in their use.
16 So I think that it wouldn't be wise to put
17 a ban on the embryonic source at this point, and wait
18 until another avenue is assessed. The length of time
19 is going to be too long.
20 PROFESSOR SANDEL: Can you be more
21 specific? Are there certain types of research avenues
22 that you would associate more with embryonic stem cell
23 research, as against adult stem cell research?
24 Is it likely that success is in particular
25 areas, or is it just that you feel that as a general
1 matter it is better to have more avenues rather than
3 DR. GEARHART: Well, I think that one of
4 the messages that I hope that I can get across, and
5 maybe Catherine will, too, is that we are in very
6 early stages in all of stem cell research, no matter
7 what the origin of the cells are.
8 And to make a judgment as to which of
9 these is already more advanced than the other, it
10 would be a tenuous one at this point, because you have
11 got to remember that there are very few investigators
12 actually working on embryonic stem cells at this
14 The list on the adult side obviously is
15 larger. I mean, as far as investigators are
16 concerned. And I don't think that any of us are
17 really showing dramatic -- you know, utilization in
18 the sense that we can say we are going to go to any
19 clinical use of this.
20 It is going to take years for this to
21 occur. We are in the very early stages and so I would
22 be really hesitant to say that anything is
23 demonstrating anything better.
24 All I would say about embryonic stem cells
25 at this point in a very positive way is that we know
1 that at this point that out of these cells we can
2 virtually generate any cell type we want in dish and
3 in large numbers.
4 That is the advantage of this approach.
5 Now, whether this will be surmounted by other
6 discoveries in adult stem cells to do the same kinds
7 of things, I don't want to predict. I hope that it
9 You know, our -- and I also want to
10 emphasize that we -- and although we are associated
11 with the embryonic form, we are studying other forms
12 as well. We are not foolish.
13 As a scientist, you know, you are not
14 going to put all your eggs in one basket here. And so
15 we are trying to move forward on a broad front, and I
16 think that this would be the more rational way to
17 proceed in this arena.
18 DR. KASS: Frank.
19 PROFESSOR FUKUYAMA: Dr. Gearhart, did I
20 understand you correctly that in the experiment that
21 you headed up with the mouse that it lost the motor
22 function in its rear legs, that you were injecting
23 human stem cells?
24 DR. GEARHART: Yes. Well, if I could
25 correct you a moment. It was a rat, first of all.
1 PROFESSOR FUKUYAMA: Okay. A rat.
2 DR. GEARHART: Rat, too, but the issue is
3 please don't say that you are injecting stem cells.
4 These are derivatives of stem cells. I mean, just so
5 that we know, but they are out of the stem cell line,
7 PROFESSOR FUKUYAMA: Okay. Fine. But
8 what was the resulting tissue? It was a mixture then
9 of rat and human neurons, or do you think it was
10 simply the stimulation of these other factors that was
11 causing the rat neurons?
12 DR. GEARHART: Right. That is a good
13 question. We still don't know -- I mean, to be honest
14 with you -- what the mechanism of recovery here is.
15 We know that sitting in the ventral horns of these
16 animals, and where these big neutrons reside, you now
17 have a mosaic population of host cells, of neurons,
19 I mean, we all -- I mean, human and rat,
20 or human and mouse, depending on which one we did. We
21 don't know the relative contributions. We can count
22 cells, but really what is the functional basis of what
23 occurred there.
24 We know that the human cells are also
25 rescuing the other, but to what degree. This is where
1 the hard work comes in. What was the mechanism, and
2 what really went on or is going on in that ventral
4 I can tell you in work that John McDonald
5 has done at Wash U, in which they generate a contusion
6 injury in the spinal cord of a mouse or a rat, and
7 then infuse in mouse embryonic stem cell derivatives,
8 and that he is faced with the same issue. He can see
9 that these animals recover to a certain degree, but
10 the mechanism of what is it, of what has really
11 occurred there, is not known.
12 And I think what we are going to find is a
13 demand that we come up with mechanism in some of these
14 animal models so that we can completely understand
15 what that therapy is going to be if you take it to a
17 And this is going to require a lot of
18 work. Now, some of it you could argue is that you
19 could do it all within animal studies. You know,
20 mouse embryonic stem cells, and you don't have to put
21 the human in.
22 But I think we are finding enough
23 differences between species that it would warrant at
24 least the study also of the human derived cells in the
25 same paradigms to ask those questions.
1 PROFESSOR FUKUYAMA: But I am just
2 curious. Are you getting actual tissues in which you
3 have cells from different species that are growing
5 DR. GEARHART: Oh, yes, absolutely. Yes,
6 sitting in the same -- well, you can see in the
7 section here that might be 15 or 20 microns across,
8 you see a mixture of the rat cells or mouse cells, and
9 human cells, functioning.
10 You know -- I mean, this isn't uncommon.
11 We do interspecific grafts a lot in experimental
12 things, and the question is when you do it, and we
13 see, you know, human cells growing in animals very
14 nicely. I mean, as long as there is immunosuppression
15 and things like this occurring.
16 PROFESSOR FUKUYAMA: But could you go the
17 other way, also injecting stem cells from other
18 species into human beings?
19 DR. GEARHART: Oh, yes. I mean, this is
20 one of the issues with xenografts. You know, is this
21 something -- well, there is a report recently about
22 chicken embryonic stem cells, and the fact that people
23 who had derived these were promoting the use in
1 Pig stem cells, you know, et cetera, and
2 so it can be done, but a couple of issues, and one of
3 them is the issue of the xenograft itself, of bringing
4 in endogenous viruses, and is this a wise thing to do.
5 And the other thing that I would ask you,
6 and I won't be flippant about it, is to say that if
7 you -- and one of the concerns that we have that maybe
8 this council and others would take up, is long term in
9 a neurologic sense.
10 If you are putting stem cells in, and you
11 are putting them in between different human beings,
12 what are you doing to that individual. And I would
13 say to you that if you have a stroke, and someone
14 comes along and says, well, we have pig, cow, mouse,
15 human, take your pick, what would you select.
16 I am not being flippant about it, but I am
17 just saying that I think that we know that human would
18 be preferable at this point in time.
19 DR. KASS: Could I ask a question, and
20 just for clarification again also on your own
21 experiment that you showed us. You said that some of
22 the rats were immunosuppressed and some were not. Is
23 that correct?
24 DR. GEARHART: Yes.
1 DR. KASS: And were there functional
2 differences in the results between those two groups,
3 and would that bear upon the question of whether or
4 not the major effect was owing to the action of the
5 human cells, or a stipulation of the endogenous cells?
6 And lastly, if these animals had come to
7 post-mortem was there a difference? Was there
8 rejection in the non-immunosuppressed animals of the
9 human cells?
10 DR. GEARHART: It is important to keep in
11 mind the time frame that these experiments are done
12 in. They are of very short duration relatively
13 speaking, in a period of several months maximum.
14 In experiments that have been done in our
15 laboratory, principally by Mike Shamblott, in taking
16 human cells and grafting, and these are insulin-
17 producing cells, and we have done it in a variety of
18 tissues into rodents, you always see reactive cells,
19 which means that you are eliciting an immune response.
20 Again, they are short term, and whether
21 you are getting destruction, we see cellular debris,
22 and we see this kind of stuff at these sites. I
23 should tell you a little bit that may be enlightening.
24 When you do grafts like this, if we say we
25 are putting in 300,000 cells or we are microinjecting
1 in a lot of these cells, many of these cells will die
2 at the time of injection, simply because you have
3 taken them out of one environment and you put them
4 into another, and you see a tremendous amount of cell
6 Very few of these populations of cells
7 continue to divide. In other words, it may undergo
8 one more round of division, and they sit there.
9 You do see when you come in finally to
10 look at where is the human versus where is the rodent,
11 and you use your human markers. You invariably find a
12 group of cells that you can't phenotype, if you know
13 what I mean, and to say what has happened here, and
14 clearly there are cells being destroyed.
15 DR. KASS: Fused?
16 DR. GEARHART: Well, we don't know that.
17 And one of the arguments for many years has been that
18 the central nervous system is an immune privileged
19 site. I don't think anymore that this is something
20 that is believed or subscribed to, and if you have the
21 option of immunosuppression, or of getting around
22 that, that that would be preferred.
23 And particularly when you are talking
24 about a graft going into a human being that may be
25 there for 20 years, as opposed to a matter of a few
1 months. So I think that this is going to remain a
2 major issue, and there is no question about it.
3 DR. KASS: Thank you very much. Bill
4 Hurlbut and then Paul McHugh.
5 DR. HURLBUT: John, I hear you saying that
6 we should pursue all lines of research, but I want to
7 weigh the different options here and pursue the
8 question of if the lines were restricted what would be
9 gained or lost.
10 Specifically, I have several questions
11 that hinge each on the other. First of all, the cells
12 that were implanted or tested for their tumorigenicity
13 effect that you spoke of in your paper were the so-
14 called EBDs.
15 Were those derived only from embryonic
16 germ cells; is that what is implied there?
17 DR. GEARHART: Yes. In our paper, we took
18 the stem cell itself and plated it out in a variety of
19 culture conditions, some of which are designed to
20 enhance or select for certain types of
22 And we referred to these as embryoid body-
23 derived cells. They came out of this little cluster,
24 and in our field it is essential that we take the stem
25 cell off the dish, and let it form into a little ball,
1 and which is just a multi-cellular structure, called
2 an embryoid body.
3 Now, this was an unfortunate name that was
4 given to it by a French pathologist back in the '30s,
5 but as you can imagine, when someone in a political
6 sense talks about an embryoid body, they conjure up
7 embryos here.
8 But these are little clusters of cells,
9 and within those or within that cluster, the beginning
10 of differentiation begins. These cell-cell
11 interactions are essential for this. We have not been
12 able to mimic this in a sheep yet.
13 So what happens is you get within that
14 ball a variety of cell types being formed, and all
15 that you want to do is to disassociate that ball after
16 a period of time, and select out only those that are
17 going in the direction that you want them to go in.
18 So this is what we did in that experiment,
19 and so we have now these EBD lines, and in these
20 lines, in these human lines, and these lines have been
21 placed in a large number of animals, in the grafts
22 that we have used, we have never seen a tumor up to
23 this point.
24 And it may be unique to humans, because
25 human primary cultures are easy to establish and mouse
1 aren't. I mean, there is an issue here that we don't
2 know that you can't do the same experiment in the
4 So with our experience with the EBDs, we
5 have never seen a tumor. Our experience in the mouse
6 and using what we thought were equivalent lines, we
7 have seen too many tumors with respect to grafts into
8 the central nervous system.
9 DR. HURLBUT: Just parenthetically haven't
10 I been reading all along that embryoid bodies are also
11 formed from ES cells?
12 DR. GEARHART: Oh, yes, absolutely.
13 DR. HURLBUT: But the point is that your
14 particular lines don't produce tumors, and the ones
15 derived from the primordial germ cells don't seem to
16 produce tumors; whereas, the embryonic stem cell lines
18 DR. GEARHART: Well, the only comparison
19 that we have at this point are mouse ES lines, in
20 which we have derived different types of precursors
21 under different conditions, have been compared to
22 human EG lines that have been derived, or which
23 precursors have been derived in a slightly different
1 You can't derive them both in the same
2 way. We have seen nothing up to this point on human
3 ES derived lines transplanted. We just have not seen
4 any data on that.
5 So I don't want to make it clear that
6 there is a difference between the derivation either
7 from a germ cell derived, or an inner-cell mass
8 derived line. Does that make sense? That comparison
9 is not there yet.
10 DR. HURLBUT: Well, obviously what I have
11 been getting at here is if in fact your cell lines are
12 less likely to cause tumors, then does that imply that
13 there might be some advantage to using your cell
14 lines, and if so, would it in fact be the greatest
15 advantage if a patient's own cell line could be
16 derived from primordial germ cells?
17 DR. GEARHART: Oh, boy, this committee
18 would -- well, wow. Now, think what this means. It
19 means that you would be generating an embryo, and
20 having it implanted. Now, what you don't know is that
21 our fetal tissue comes from 5-to-9 weeks post-
22 fertilization. These are therapeutic abortions.
23 And which means now that you are way
24 beyond -- I mean, the point of where a blastocyst is,
1 and obviously way beyond I think anyone subscribing to
2 that approach.
3 DR. HURLBUT: You told us that in your
5 DR. GEARHART: Okay.
6 DR. HURLBUT: But is it true that maybe
7 there would be some great advantage if we could find a
8 legitimate way to harvest tissues generated from a
9 specific patient at a later date?
10 DR. GEARHART: Right. Well, I think it
11 would be terribly risky. We have been asked this
12 question a lot though; is it possible to do a biopsy
13 on a developing embryo, and to remove just a few germ
15 I think at the stage that we are using
16 these embryos are a matter of -- or fetuses are a
17 matter of maybe 6 or 7 millimeters in length, and to
18 do the surgery on this I think would just be
19 impossible without causing harm.
20 The other issue that I would contend is do
21 you think it would be okay to go in and remove the
22 germ cells from an embryo and let that individual go
23 on and say, well, we have taken your germ cells. Now,
24 we have another therapy for you.
25 And so I don't think it is a very good thing to do.
1 DR. HURLBUT: And that is my final point,
2 and I wanted to ask you personally in working with
3 these cells, do you see 14 days as some kind of magic
4 marker moment?
5 Do you see something crucial about
6 implantation? And you spoke of keeping all options
8 DR. GEARHART: Right.
9 DR. HURLBUT: Why in fact do we allow
10 abortion fairly late in term, and yet now we are
11 speaking as 14 days as the sacred moment? I know that
12 I am opening a very difficult issue here.
13 But in fact wouldn't we gain a lot
14 scientifically from extending that 14 day limit
15 potentially if we could find a culture median that
16 could sustain the embryo, or wouldn't we gain a lot
17 from implanting, even gestating and harvesting?
18 And why do we feel that we shouldn't do
19 those things? And I would also be interested in your
20 personal response to these ethical issues.
21 DR. GEARHART: Wow, you have asked a lot.
22 As you know, stem cells have been obtained from many
23 stages of human fetal development, and have been found
24 to be useful in generating various cell types in
1 And if we look at a variety of studies,
2 you can find it in the published literature. We have
3 had a number of requests for fetal tissue at different
4 stages, and I think legitimate requests of
5 investigators willing to investigate cell lineages, et
6 cetera, within the embryo.
7 So people have been thinking about it. I
8 mean, there is no question about that. We have found
9 it difficult enough to be fortunate enough to obtain
10 the fetal tissue that we work with.
11 I mean, there is a consenting process and
12 we have nothing really to do with other than to make
13 sure that it complies with institutional, Federal, and
14 State law.
15 To obtain viable tissue from abortuses of
16 any kind is a major concern. When we started our
17 studies, we looked into using spontaneously aborted
18 material, which occurs across the board, but mainly in
19 the early stages.
20 And we thought that this would be a good
21 source. As it turned out, by the time that we were
22 notified -- and this occurs in outlying hospitals, and
23 not at major medical centers, where investigators are
24 -- you know, a patient presents with a miscarriage,
25 and it is taken care of in the ER.
1 And it turned out that it was very
2 ineffective, number one. And, number two, and then I
3 will get back to your question, we found that most of
4 the material that did come to us had chromosomal
5 abnormalities that made it less desirable for use.
6 Now, the issue of the 14 days, and what
7 does it mean. Well, this was something that really
8 came into play in the United Kingdom when they were
9 trying to deal with this issue.
10 And it was decided at that point that at
11 that stage the embryo still does not have a central
12 nervous system. It can feel no pain, et cetera. And
13 this was why basically that period of time was set to
14 be able to grow them in culture, or to remove tissue.
15 We, as embryologists, argue the point all
16 the time as to what is going on in these early stages,
17 and we were always asked these questions. When do you
18 believe personhood occurs and when is it established,
19 and things like this.
20 To me that is not a biologic question. We
21 don't have a means of probing that. So I think that
22 is why the 14 days was selected, and that's why it is
23 sort of adhered to in a sense.
24 Do I adhere to that? Well, to a certain
25 degree, no. We take material that is later on, and it
1 is cadaveric fetal tissue. I think that we should be
2 able to utilize any tissue that comes out of abortion
3 if the alternative is that it is just going to be
4 disposed of, which is what happens.
5 The pathologist takes a look at it to make
6 sure that all of the parts are accounted for, and
7 there is an issue about being concerned about what is
8 left in the uterus.
9 That is my personal opinion on that. But
10 I don't think that we should be going and establishing
11 pregnancies, and to downstream then utilize that
13 I mean, to then stop the pregnancy and
14 then to recover it. I mean, that is my personal
15 opinion. I don't think we should be doing that. As
16 you know, years ago, President Reagan was faced with
17 this, I believe, when he heard that families were
18 establishing pregnancies so that regions of the brain
19 could be harvested to treat Parkinson's disease in the
21 And clearly we don't subscribe to that in
22 any fashion.
23 DR. KASS: Thank you. We are coming up to
24 the break and I have Paul McHugh, Mike Gazzaniga, and
25 we are running a little late because we started a
1 little late. We will take a break shortly. Paul and
2 then Mike.
3 DR. MCHUGH: My point is very brief, John,
4 because you have touched upon it in several places.
5 But first of all, I want to thank you very much for
6 that coherent presentation, and I especially thank you
7 for showing us experimental data.
8 And that is what of course generates
9 better questions to ask you. And it is really out of
10 that experimental work that I did have a question.
11 And that is what you showed us was fundamentally a
12 xenograftic experiment using human tissue, human
13 cells, in rats.
14 And the results were very interesting, and
15 not only was there growth of cells, but you told us
16 that there were trophic factors that were probably
17 acting in this way.
18 And I then wondered, and you can answer
19 this, why was it necessary to use human cells to
20 demonstrate this phenomenon in a rat, and why weren't
21 you using rat cells to do rat experiments.
22 And if that is true, that you could do rat
23 cells to do rat things and the like, the development
24 of the question is would it not be wise of us to ask
25 you all to go back and work with your rats and your
1 mice, and your cats and your sheep, and keep going at
2 it, and come back and tell us why you need human stuff
3 to do this stuff, okay?
4 DR. GEARHART: Okay. We did it first with
5 mouse cells. We don't have rat embryonic stem cells.
6 We did it first with the mouse and it worked.
7 And in our exuberance, saying, well, would
8 the human cells work, and they did. There is no
9 question that I think that the mouse cells worked
10 better, and the mouse cells were from these neural
11 precursors that we had obtained that I had mentioned
12 that we had this concern about tumors.
13 But they did work, and so the only two
14 cell types that we have found at this point that work
15 have very similar origins if you know what I mean.
16 Clearly the paradigm has to be extended to
17 other sources of stem cells, adult and umbilical, and
18 this is planned to say in this particular paradigm
19 will it work.
20 So, Paul, the answer is that we did it
21 first with the rodent cells, and we could pursue that.
22 I mean, as far as looking for the growth factors and
23 what not.
24 But we have changed almost completely to
25 the human cells for trying to determine what those
1 growth factors were that were secreted, but we could
2 do that again with the mouse, absolutely.
3 DR. KASS: Mike.
5 DR. GAZZANIGA: Just briefly, thank you
6 again for a wonderful presentation. This moves to
7 another level, and that is how big is the American
8 biomedical engine.
9 And I ask that from the sense of having
10 just taken a trip to China and Japan, and England, and
11 you read that Sweden and Singapore, and India, and so
12 forth, are going ahead.
13 If America dropped out of this for legal
14 reasons that are on the horizon, how big an impact
15 would that have on the overall resolution and
16 development of these therapies?
17 In other words, if you just look across
18 molecular genetics and microbiology now, and prior to
19 this issue arising, what is the size and importance of
20 the American effort?
21 DR. GEARHART: Well, I don't think that
22 there is any question that the investigators funded
23 through the National Institutes of Health, and our
24 academic establishments here, are the engine that
1 drives biologic research, biomedical research, in the
3 There is no question about it. I mean,
4 the volume, the sheer volume of this, is enormous.
5 And if you look at this compared to even in our
6 country to what the biomedical industry, or I mean the
7 private industry is putting into this, it is dwarfed
8 by the Federal funding.
9 And this is really what is enabling and
10 this is why I think the U.S. has been so far ahead.
11 So it is essential I think to have Federal funding
12 into this area really to reach our goals as quickly as
14 There is one last thing or one thing that
15 I would like to say to the committee, and it is
16 understandable, but when you are in and start in a
17 business like this, you don't know the impact of it.
18 The thousands of communications that we
19 have received from patients, and patient-based groups,
20 about our work and about moving the work along, not
21 only is it emotional, it is unbelievable. I mean,
22 from the standpoint of just pure numbers, sheer
24 It doesn't just extend within the United
25 States, but throughout the world. In 1998 when we
1 published our paper, within a few days we had 10,000
2 e-mails alone about it.
3 And every day I still get hundreds of e-
4 mails relating to this. It extends not only to bona
5 fide -- you know, many people don't understand what
6 this work is about.
7 They are contacting you for a brain, or a
8 uterus, or from some countries we have had requests,
9 hundreds of requests for penises, for example. And
10 you are trying to figure out why -- you know, what is
11 the issue here.
12 We need education and we need informing to
13 say that we are dealing really with cells and tissues
14 at this point. That is what we are really about. It
15 is going to be years away before it goes beyond that.
16 And so what I am trying to say is that
17 there are requests throughout the world. So that is
18 one issue. I mean, the pressure is enormous, and also
19 people offering you large sums of money to provide
20 them with cells outside of the arena that it should be
21 done in. Do you know what I mean?
22 There is desperation, and you see this,
23 and it is tragic, and as a researcher this is new to
24 you. This is something that you are not accustomed to
25 and never will be accustomed to handling.
1 So I just wanted to let you know what that
2 pressure is like. It is enormous. I have boxes full
3 of these things. I don't know what I am going to do
4 with them, but you try to respond.
5 There has been an issue with brain drain.
6 We know that there has been one investigator from the
7 University of California system that went to the U.K.
8 and received one-and-a-half million pounds to pursue
9 this work in the U.K.
10 Well, this happened here. I will tell you
11 that -- and I am talking to students in our own group,
12 you know, go to Europe for your post-doc, and go to
13 England for your post-doc if you want to continue in
14 this thing.
15 And I think you will see more of this, and
16 whether major investigators will leave, I don't think
17 so. I think we will get through this, and I hope that
18 we will get through this period in this country.
19 There are many, many investigators, many
20 investigators, and I can't tell you what it is like
21 not to be able to give a cell to the person next door
22 to you because of a policy.
23 I mean, this is just an incredible
24 situation. I think we will get through it, and I
25 think we will be okay. But I am still concerned about
1 it. Sorry for the editorial, but I think it is
3 DR. KASS: Charles, did you want a quick
5 DR. KRAUTHAMMER: If I could just ask a
6 very quick question. You said that you would oppose
7 and you supported the opposition of creating a fetus
8 for, say, harvesting the brain cells, and you talked
9 about the example in the Reagan years.
10 On the other hand, there is no difficulty,
11 at least in your estimation, of using tissue from a
12 discarded fetus already aborted, and tissue which
13 would otherwise be thrown away.
14 Would you apply that same distinction to
15 the embryonic stage? In other words, you now use --
16 you develop embryonic stem cells from discarded
17 embryos from IVF clinics, and would you be equally
18 opposed to the creation of embryos specifically for
19 their use as sources of embryos using that same
21 DR. GEARHART: No, I would not be opposed
22 to that. I don't give the same moral status to that
24 DR. KASS: Well, we have -- let me just
25 make mention of one matter. Janet Rowley has
1 submitted in writing, and I would endorse, these
2 questions if we had enough time.
3 We would like your comments on what kind
4 of regulation you think might be or should be
5 developed for this area, and what is the status of
6 government support for what kind of research, and what
7 are the limitations that are counterproductive.
8 If we could invite -- if you would be
9 willing, and these are hard questions and they are big
10 questions, but if you would be willing to respond if
11 we put these set of questions to you, and perhaps some
12 others to you in a letter?
13 DR. GEARHART: Absolutely.
14 DR. KASS: I think the committee would be
15 very grateful for your help in thinking through the
16 regulatory questions, which are at the moment not what
17 we have here.
18 DR. GEARHART: Absolutely.
19 DR. KASS: I just want to thank you very,
20 very much, for an instructive morning, and also for
21 the wonderful spirit in which you presented your
22 remarks and engaged the questions. I am very grateful
23 to you for coming.
24 We are running about 15 minutes behind,
25 and we will reconvene at a quarter-of. We have an
1 hour-and-a-half for the second session this morning as
2 originally planned.
3 (Whereupon, at 10:33 a.m., the council was
4 recessed and resumed at 10:49 a.m.)
5 DR. KASS: Would the members please rejoin
6 the meeting. While we are waiting in the hope that
7 our straggling colleagues will arrive, a couple of
8 matters of business.
9 If anyone has not turned in a request for
10 a box lunch, please do so now, and that should be in
11 front of you. We will have lunch in the room just
12 down the hall where we gathered before.
13 The photographer who has been around here
14 is doing individual photographs for the commission and
15 he will want to take individual photos of members, and
16 we can do that in connection with lunch.
17 And you will also have in front of you in
18 addition to the materials that Dr. Gearhart provided
19 us, which by the way is -- and the lights were out and
20 so you couldn't see, but one could recapitulate his
21 talk with the help of the figures here, as well as
22 checking his article in Nature.
23 But you also have in front of you a
24 revised version of Bill Hurlbut's memorandum. This
25 has been updated and corrected, and he would like us
1 to substitute it for the one that was sent around
2 earlier this week. Is that correct, Bill?
3 DR. HURLBUT: Yes.
4 DR. KASS: All right. Well, again, it is
5 a great pleasure to welcome Dr. Catherine Verfaillie,
6 from the University of Minnesota. You have her
7 curriculum vitae in the briefing book, which you can
9 I won't waste any more of her time by
10 reading from it, and just simply allow her to help
11 educate us on the prospects of present and projected
12 of adult stem cells for regenerative medicine.
14 DR. VERFAILLIE: Good morning. I would
15 also like to start out and thank Dr. Kass and the
16 council to allow me to present this information on new
17 findings in adult stem cell biology which have been
18 received with great excitement, and correctly so. If
19 they are, and they are actually set upside down, the
20 classical paradigms of biology, and so to be able to
21 do that you have to have full proof to actually be
23 able to be in a position like that.
25 If they are, and they are actually set
26 upside down, the classical paradigms of biology, and
1 so to be able to do that you have to have full proof
2 to actually be able to be in a position like that.
3 As Dr. Gearhart already gave in his
4 previous eloquent description of what stem cells are
5 and what they can do, and we will get back to that to
6 some extent at the end, although we are far away from
7 actually being able to use adult stem cells for
8 clinical applications.
9 But what I would like to do is give you an
10 overview of the greater potential of adult stem cells,
11 which has always been termed adult stem cell
12 plasticity, and what we do know and what we don't
14 And where this may actually lead us. Dr.
15 Gearhart also indicated that embryonic stem cells in
16 humans are fairly or very much in their infancy, the
17 same as we are for adult stem cell biology, too, and
18 so I don't think we are anywhere close to be able to
19 come up with new therapies at this point in time.
20 I would also like to reiterate that even
21 though my laboratory and our group works on adult stem
22 cells, we have actually actively pursued investigators
23 in embryonic stem cell research, human embryonic stem
24 cells, just so that within the same institution we
25 would have laboratories that have one cell, and other
1 laboratories that have the other cell, so we would be
2 in a position to compare and contrast the potential of
3 the different cell populations, and I think that is
4 very important.
5 With that, I will actually start my
6 presentation, and I will point out that the work was
7 mainly funded through the NIH, since it is all adult
8 stems that we are working on, and not embryonic stems.
9 And also a number of foundations and one
10 pharmaceutical company.
11 Dr. Gearhart already gave you an overview
12 of where embryonic stem cells come from, and where
13 primordial germ cells or stems come from. And I am
14 going to reiterate that for you.
15 I just put up this cartoon that Dr.
16 Weissman published two years ago in Science to point
17 out a couple of things. During development, cells in
18 the inner cell mass make sequential decisions, and
19 each of these decisions is actually accompanied with
20 gain of function, but also loss of function.
21 The gain of function is that the cells
22 learn how to become a more specified cell type; and on
23 the other hand, actually lose the potential to become
24 other cell types.
1 And so the decision to be made is somatic or
2 germ cell, and within the somatic lineage doing
3 something that is called gastrulation, cells decide to
4 become the different parts of our body, whether it is
5 endoderm, which is the internal organs, mesoderm,
6 which are limbs and soft tissue, and ectoderm, which
7 really comprise the skin, the central and peripheral
8 nervous system.
9 And within each of these groups cells
10 again make decisions and learn how to become stem
11 cells for specific organs. And the stem cells for
12 specific organs that has been most well studied is
13 actually the hematopoietic stem cell, which is
14 currently extensively being used in clinical
15 applications for bone marrow transplantations or
16 peripheral blood stem cell transplantations, or cord
17 blood transplantations.
18 And so that actually has set the paradigm
19 on how we decide what stem cells are. Aside from
20 hematopoietic stem cells or blood stem cells, we have
21 a number of investigators who have identified tissue-
22 specific stem cells in a number of different organs,
23 including for instance the brain, which we until about
24 10 or 20 years ago thought was a final product when we
25 were born.
1 But it is now clear that there are stem
2 cells in the brain that can recreate neurons and other
3 components. There is also stem cells in the liver,
4 and stem cells in the gut, and there is stem cells in
5 the skin, and so forth.
6 The reason why I put this slide up is
7 actually to point out that these arrows have always
8 gone down, and so we have always thought that each
9 time a cell decided to learn something new that it
10 lost the capability of doing something else.
11 And so if we envisioned beforehand that
12 the arrows would be reversed, we thought that was
13 possible, but we associated that with classical
14 transformation, or actually cancer-forming cells.
15 So what do we know about hematopoietic
16 stem cells and that is really the paradigm to which I
17 am going to try to talk through the whole field of
18 adult stem cells.
19 In hematopoietic stem cells, we can
20 actually take a single mouse bone marrow cell that we
21 characterize by proteins on the cell surface, and take
22 that single cell, and for instance you can take it
23 from a mouse that is engineered to fluoresce green
24 under a specific light, and put that in a regular
1 mouse, and ask whether they can reconstitute the blood
2 elements of that animal.
3 And a number of investigators have
4 actually been able to do that. You can take a single
5 cell, and give it to a mouse that was lethally
6 irradiated so it has no blood, and this cell can
7 recreate the red cells, the white cells, platelets,
8 lymphocytes, for the lifetime of that animal.
9 And that is really the proof that you have
10 a stem cell that can self-renew, and a single cell can
11 make multiple different things, and it can repopulate
12 functionally the organ that it needs to repopulate.
13 And so that is really the criteria that we
14 have to hold ourselves to, to actually talk about stem
15 cells, and if you talk about plasticity, you will have
16 to hold us on the same criteria and showing that a
17 single cell can now make two tissues, and that this
18 cell can make two tissues from a single cell, and that
19 these new cells can repopulate a tissue functionally
20 in vitro.
21 Now, over the last 5 or 6 years, there has
22 been an enormous number -- well, not an enormous
23 number, but probably 40 or 50 papers now that have
24 come out in the scientific publications that have used
25 the word adult stem cell plasticity.
1 And what is meant by that is that you take
2 a cell that was supposed to be a one cell type. For
3 instance, you take a bone marrow cell, or you take
4 cells that are enriched for hematopoietic stem cells.
5 And it appears that some of these cells
6 may acquire characteristics of cells outside of the
7 organ where they came from. And so it has been shown
8 for bone marrow cells, or cells enriched for
9 hematopoietic cells, that if you transplant these into
10 an animal that was irradiated, and you look in tissues
11 outside of the blood, that you can actually find, for
12 instance, skeletal-muscle cells, heart muscle cells,
13 or endothelial cells, that are now derived from this
14 donor hematopoietic cell.
15 There is also papers that have shown that
16 if you take muscle from an animal and mix it up in the
17 laboratory, and culture it for a few days, and then
18 use the muscle tissue to give back to an animal, that
19 you could reconstitute the blood system in that
21 Now, if you think in anatomical terms,
22 this is still within one of the three categories that
23 I gave you at the beginning; mesoderm, endoderm, and
24 ectoderm, and all of this is still within the
25 mesoderm. So this is maybe not so hard to understand.
1 However, there is also papers that two
2 different cells from bone marrow, hematopoietic cells,
3 and zymogenic cells, which are cells that make bone
4 and cartilage, can give rise to cells that appear to
5 have neuronal characteristics, both neurons and glial
6 cells, that support the structure of the brain.
7 And there is a number of studies that have
8 shown that bone marrow cells can contribute to liver,
9 skin, lung, gut, and so forth, and so you can pretty
10 much put arrows in whichever way you want.
11 You know, people have published data that
12 suggests that indeed this may be possible. So
13 obviously this goes against our paradigms and this
14 would say that either something strange is going on,
15 and just something in the last few years is something
16 that we have actually identified.
17 Now, if we want to talk about blastocyst,
18 I started out with the paradigm of stem cells, and so
19 there is multiple different possibilities here.
20 Either the bone marrow, which seems to be
21 the organ that harbors the most of these cells,
22 harbors many, many different stem cells, and it
23 harbors the hematopoietic stem cells, but it also
24 harbors the neuro stem cell, and the liver stem cell,
25 and so forth.
1 And which that would not be bad, but that
2 truly would not be a single stem cell that could be
3 expanded and used to actually transplant patients with
4 all kinds of different organ diseases.
5 A second possibility is that somehow the
6 cell can be "de-differentiated" and redifferentiated,
7 depending on the environment that it is put in, and
8 that the hematopoietic stem cell can learn how to
9 become a liver if you put it in the liver, or it can
10 learn how to become a brain if you put it in the
12 Or it could be that it is a remnant of
13 embryonic stem cells or the primordial germ cells that
14 you heard about from Dr. Gearhart that are left around
15 in the body, and that under specific circumstances can
16 be reactivated and contribute to tissues.
17 And the issue of fusion has been brought
18 up because of the two papers recently in Nature, and
19 the possibility is in theory that what we see is
20 actually that.
21 For instance, a hematopoietic stem cell
22 fuses with a liver cell, and now you actually have
23 something that is a hybrid, but it has actually liver
1 The other questions that I am going to try
2 to address, and I don't have all the answers for this,
3 is this actually clinically relevant? You know, if
4 you transplant bone marrow into a patient and you find
5 two liver cells that are derived from the patient,
6 from the donor, it doesn't necessarily mean that that
7 is going to help anybody down the line.
8 So the graft has to be robust and
9 persistent, and there has to really be proved that we
10 don't just see cells that look like a tissue that they
11 end up in, but they also have to function like a
12 tissue that they end up in.
13 And then the question that I will bring
14 back up at the end, the first question, what is
15 plasticity, and will that matter from a clinical
17 And so we started out in this field -- I
18 am a hematologist, and I do bone marrow
19 transplantation as my clinical profession, and I have
20 been interested in hematopoietic stems in the bone
22 And about six years ago somebody in our
23 group asked me whether we could grow mesenchymal stem
24 cells, which are cells that may grow on cartilage, to
1 treat children with a specific genetic disease called
2 Hurler's disease.
3 And when we did this, mesenchymal stems we
4 happened to find, and we went about trying to create
5 these to be in compliance with GMP qualifications,
6 meaning we were trying to remove all sera out of the
7 system, and yet we were trying to use very well
8 defined culture systems.
9 And so while we were doing this, we came
10 up with a cell that you have heard Dr. Kass refer to
11 as a multi-potent adult progenitor cell, because we
12 don't have a much better word for it.
13 And it will be appreciated as MAPC, and
14 which appears to have a much greater possibilities
15 than the mesenchymal stem cell possibilities. So we
16 take these cells from bone marrow from humans, and we
17 can also take them from mice and from rats.
18 And you place these in a culture system
19 that is very well defined, and ingredients, and growth
20 factors, and no serum, and low density, and we expand
21 the cells as much as we can by splitting the cultures
22 on a regular basis.
23 And if we do this, we have actually found
24 that these cells appear to have an enormous growth
25 potential. And so here on the left-hand side would be
1 bone marrow from an individual, and we start with
2 about 10cc's or a spoon of bone marrow, deplete all
3 the blood elements from the bone marrow, and put it in
4 a culture dish, and then grow the cells for long
5 periods of time.
6 Classical adult cells would actually not
7 expand much more than 50 times or 60 cell population
8 doublings, just because we have a clock inside the
9 cell that actually causes the cells to become
10 senescent or old once they go beyond a certain number
11 of cell divisions.
12 And so in the human system, as well as in
13 the mouse and the rat system, we have been able to
14 show that we can create or grow cells that do not seem
15 to conform to this internal aging clock.
16 And the cells can go beyond that and the
17 human cells are now close to a hundred population
18 doublings, and in mouse and rat, over 150 population
20 If you look at the aging clock itself,
21 which are the telomeres, the telomeres are long and
22 they do not seem to shorten in culture, which goes
23 again with the idea that the cells do not senesce in
1 So in this respect, they have
2 characteristics that are similar to what you would
3 find in embryonic stem cells, but also this internal
4 clock is actually not working.
5 The phenotype of the cell is strange, and
6 it doesn't really fit anything in particular, but
7 there is definitely no characteristics in these cells.
8 These cells are blood hematopoietic stem
9 cells, and I am not going to go through all the
10 details here, but if you do an extensive phenotype
11 characterization of the cells, they don't look like
13 They have some characteristics of
14 embryonic stem cells, but there are a lot of other
15 ones that they do not have. So they have some genes
16 that are turned on that are present also in embryonic
17 stem cells, which are the top two here, and then they
18 have on the cell surface antigens that you really only
19 find on embryonic stem cells, or primordial germ
21 So in some respects again these cells have
22 some features of embryonic stem cells, even though we
23 got these from the bone marrow of humans, mice, and
1 We then started trying to test initially
2 all in culture dishes what these cells could do, and
3 we asked whether they could differentiate in multiple
4 different cell types.
5 And because our initial charge was
6 actually to try to grow mesenchymal cells and make
7 bone and cartilage, that is what we did first. And so
8 what we showed in the culture dish is that if we
9 switch the culture conditions around, and actually use
10 ingredients that are no longer supported for
11 maintaining the stem cells in an undifferentiated
12 state, by actually switch them such that we hope that
13 we can turn on the genetic programs to make bone or
14 cartilage, and so forth, we could indeed do this.
15 And this is no different than the
16 classical mesenchymal stems that have been described.
17 So we can induce the cells to become bone, and if we
18 say that they differentiated into bone tissue, it is
19 actually a calcified tissue at the bottom of a dish.
20 We can induce the cells to become
21 cartilage that looks like articular cartilage, even
22 though it isn't very well organized. And you can
23 induce the cells to become lipid-laden lipocytes, and
24 we can induce them to become skeletal muscle cells.
1 And these cells can actually fuse and make
2 long muscle tubes almost, and we can induce the cells
3 to express a number of muscle markers for the heart,
4 even though we haven't really seen beating cells.
5 And so we don't really know whether these
6 cells are heart muscle cells. So this is still not
7 that strange, because there is this cell in the bone
8 marrow that has been identified that can do this.
9 Now, we found three other lineages that
10 are completely outside of the mesenchymal lineage, and
11 some of this has been published, and most of it is
12 actually in press currently.
13 One of the things that we found is that
14 these cells can differentiate into cells that line
15 blood vessels, which we call endothelial cells. And
16 we have been able to show that these cells
17 differentiate into cells that look like endothelial
18 cells, but also function as endothelial cells.
19 And as shown in this picture here is
20 actually a blood vessel from an animal that had a
21 tumor underneath the skin, and we actually infused
22 human endothelial cells derived from human MAPCs in
23 this animal, and showed that these endothelial cells
24 seek out the tumor and actually help create new blood
1 vessels in the tumor, which the tumor needs otherwise
2 it can't grow.
3 And so this proves that these cells that
4 are in the bone marrow can differentiate into cells
5 that can make endothelium. More surprisingly is that
6 the cells can differentiate into cells that look like
7 neutrons, look like astrocytes, and support themselves
8 in the brain, and to some extent function like these
9 cells in the brain.
10 And so we show here that they
11 differentiated into cells that look like neurons and
12 have electrophysiological characteristics like
14 And so this is the second major layer of
15 the embryo, and then we also have been able to show
16 that we can make these cells differentiate into cells
17 that look like liver cells, and actually function like
18 liver cells in a culture dish.
19 And so this would mean that this cell
20 population, these MAPC cells, can actually
21 differentiate into all of the major components of a
22 human being, even though we only show a few cell
23 lineages here.
24 I am not going to go through this in too
25 much detail because it is highly technical, but
1 essentially we have not been able to use genetic
2 marking to prove that this could all be derived from a
3 single cell, and we don't depend on population of
5 So this fulfills two of the criteria of a
6 stem cell. A single cell can differentiate and grow
7 for long periods of time, and can differentiate into
8 multiple different tissue cells.
9 Two more sets of experiments were done to
10 try to gauge the potential of these cells. The first
11 one was done in an chimeric animal model, in which we
12 took the adult cells, and injected even a single adult
13 cell into the blastocyst of a mouse and asked what
14 would happen in this mouse, and whether we would see
15 contribution to some tissues, no tissues, or all
17 So we injected a single cell or we
18 injected 10 to 12 cells, and shown here are two
19 animals. The top one is obviously and the donor cells
20 here have a gene that if you stain it correctly the
21 cells turn blue.
22 So what we did is we let the animals get
23 born, and we looked at the animals by genetic tools to
24 try to figure out if there were donor cells in
25 multiple different organs.
1 And we also then took the mouse and
2 actually cut a thin slice through the middle of the
3 animal and asked which organs would have blue cells
4 contributing to the mouse.
5 The top mouse is an animal that if you
6 looked in the tail by genetic tools that we couldn't
7 find any donor cells, and the bottom mouse here, this
8 is its head, and over here would be his tail, and you
9 can see the spine, and the brain, and all the internal
11 And you can see that the majority of all
12 the tissues of this animal actually appear to be
13 derived from a single blue adult cell that we have put
14 into the blastocyst.
15 The efficiency isn't a hundred percent,
16 and this is shown on the bottom here, and so if you
17 look over here, and if you put in one cell per
18 blastocyst, 60 percent of the animals will not be
19 chimeric, but 30 percent or 40 percent of the animals
20 will be chimeric to varying degrees.
21 If you increase the cell number the
22 chimericism goes up. So this is probably not quite as
23 good as embryonic stem cells, but it is a fairly
24 significant degree of chimericism, and actually the
25 frequency appears to be one in three cells.
1 So this would suggest that the cells can
2 probably make under the right circumstances more cell
3 types than we have be able to prove in a culture dish.
4 We can also ask if we now take these stem
5 cells and give them to a mouse that is born, and we
6 give here again cells from the donors' mouse, which
7 again are blue, and we gave these to an animal that
8 was either not irradiated or irradiated with a small
9 amount of radiation therapy in the hope that maybe
10 that would help the cells engraft.
11 We used an immune-deficient recipient
12 mouse, just because we were worried that the new genes
13 that are in the blue mouse might actually be a basis
14 for rejection. So we don't know what would happen in
15 a non-immumodeficient mouse.
16 If we do this, what we found is that we do
17 find engraftment in some tissues, but not all. So,
18 for instance, in the top panel, we see that there is
19 engraftment between 3 and 9 percent in the
20 hematopoietic system of this mouse, and we can find
21 the cells, and the blood we can find in the bone
22 marrow, and we can bind them in the spleen.
23 And if we look in these animals, we can
24 also find over here, and what we did is we actually --
25 the blue color, we used an antibody that is now green,
1 and co-labeled it with a red stain that stains the
2 specific tissue.
3 And you can see in the liver that there is
4 areas in the liver where donor cells appear to be
5 present. And there is areas in the guts, in the
6 villae of the gut, where donor cells appear to be
8 And there is areas in the lung where donor
9 cells appear to be present. The presence of these
10 cells can be seen anywhere from four weeks after
11 transplantation, all the way to 24 weeks, which is
12 about six months, and the unfortunate thing with the
13 mouse model that we use is that these mice usually die
14 from lymphomas at an early age because of the
15 deficiency that they have.
16 So we really have not been able to extend
17 the cultures or have the mouse experiments beyond 6
18 months, and so we are actually trying to go further.
19 We transplant the cells in an animal that
20 is 6 to 8 weeks old, and so it is not a very young
21 mouse, and it is also not an old mouse. What we
22 showed is that if you damage certain tissues like the
23 hematopoietic system, and the gut system, that you
24 have increased engraftment, which is consistent with
1 the fact that these cells go to places where the
2 repair might be needed.
3 However, we did not see in this mouse
4 model engraftment in a number of other tissues, and
5 mind you that we gave these cells IV to an intact
6 mouse, which actually was not damaged in any way,
7 shape, or form.
8 And we don't see engraftment in the heart,
9 skeletal muscle, or brain, and these tissues do not
10 proliferate. We also don't see engraftment in the
11 skin and the kidney, and so these organs we didn't
12 really see very much engraftment.
13 However, if you infused the cells directly
14 in the muscle, which causes damage, and actually done
15 the cells in response to the local cues within the
16 muscle, appear to be able to differentiate into muscle
18 So it appears that these cells have the
19 ability and blastocyst experiment to give rise to
20 many, many different tissue types, if given post-
21 natally, and we gave them as stem cells, not as
22 differentiated cells.
23 They appear to be able to respond at least
24 in some respects to cues that are present in certain
1 organs to differentiate into the cell type that is
2 specific for that organ.
3 We have looked carefully at the cells in
4 culture and we do not see a significant number of
5 gross genetic abnormalities. We have not looked with
6 a very fine-toothed comb through whether there might
7 be some minor genetic abnormalities over time and
8 culture, and these studies are ongoing.
9 If we infused the MAPCs in animals, we
10 really do not see any tumors, and so far we have not
11 seen that there are tumors that Dr. Gearhart talked
12 about, and we also have not seen any other tumors.
13 Obviously if these cells come from bone
14 marrow there is lots of precedent on bone marrow
15 transplantations, where actually if you do this,
16 actually you do not cause tumors in patients.
17 So MAPC that we have identified in our
18 laboratory seems to be a cell that is not senescing
19 and that can be found in adult tissues of humans, as
20 well as mouse and rats, and they seem to be capable of
21 giving rise to cells from the three germ layers, and
22 it can engraft in vitro in a limited number of
24 Now, what I cannot tell is whether these
25 cells actually exist as such in a person, in a mouse,
1 or in a rat, or whether our culture condition is
2 actually such that it, quote, reprograms or
3 dedifferentiates the cells that we take out of the
4 animal, and that then acquire this much more greater
5 potential, and I will come back to that in just one
7 So we now go back to my initial definition
8 of what is plasticity, which is really at the bottom
9 of all of the adult stem cell excitement. I mentioned
10 initially that we would have to show that this is a
11 single cell of a rat, and I think the majority of
12 papers so far published have actually really not been
13 able to prove that a single cell could, for instance,
14 give rise to blood and muscle.
15 In vitro, we have evidence for that, and
16 in the blastocyst injection, we took a single cell and
17 actually found multiple different tissues. You could
18 ask, well, does it matter?
19 Does it matter if there are multiple
20 different cell types in the bone marrow, and I think
21 ultimately from an FDA or regulatory standpoint, it
22 will matter, and we will have to be able to say
23 exactly what cells that we are using to be able to
24 acquire a certain function in vitro, and so I think
25 that will be important.
1 The second question is, is the
2 differentiation or is the remnant ES, and again you
3 could say, well, it probably doesn't matter. But I
4 think at this point in time, I don't think anybody in
5 this field knows whether these are left-over early
6 stem cells like ES cells, or whether these cells are
7 cells that can be reprogrammed, and redifferentiated,
8 and dedifferentiated under certain circumstances.
9 Now, does it matter? Well, you heard from
10 Dr. Gearhart that embryonic stem cells as such, and
11 not necessarily the differentiated progeny, but the ES
12 cells themselves can cause teratomas, and even though
13 nobody in the adult stem cell plasticity era has
14 actually shown teratomas, it doesn't mean that it
15 might not happen.
16 If it is dedifferentiation, it means that
17 you reprogram or you change the genetic material in a
18 cell. But if you do that, currently we have no proof
19 that we actually change something and actually cause
20 an oncogene or something like that to be activated,
21 but that is definitely within the possibilities, and
22 that definitely needs to be looked at carefully.
23 Is it fusion? All the in vitro work that
24 has been published, including the data that I have
1 shown to you today, I couldn't prove beyond any doubt
2 that that is not based on fusion.
3 Our in vitro data, we have never co-
4 cultured things with anything. So we have single
5 cells that are deployed that can do multiple different
6 things, and so we can't really ascribe that to fusion.
7 However, in vitro, I couldn't prove it to
8 you today, and we are doing studies to try to address
9 this. I think that fusion might be the reason why
10 some studies in which a lot of pressure has been put
11 on to the system, which is essentially what those two
12 papers had to do in vitro.
13 So we have a lot of pressure exerted to
14 have that one cell survive after it fuses, and that is
15 a possibility. Also, single cells that are found,
16 rather than whole colonies, may also be the result of
17 fusion, more so than experiments where you see huge
18 colonies arise in an in vivo model.
19 And so I think we currently cannot exclude
20 the possibility that some of the data is as a result
21 of fusion. Some would say does it matter, and I think
22 it matters a whole lot, even though some investigators
23 say, well, if you fuse the cells and it functions
24 properly, it probably doesn't matter.
1 But I think ultimately that we do need to
2 make sure that we understand the whole mechanism
3 underlying everything. And is all this plasticity
4 clinically relevant?
5 And so the majority of studies published
6 to date have actually shown the very low numbers of
7 tissue differentiated cells can be found in multiple
8 different tissues.
9 A number of papers have been published,
10 two in particular. The paper by Lagasse, et al.,
11 where they show that they could rescue an animal with
12 liver failure by bone marrow transplantation, but they
13 have significant degrees of engraftment.
14 So that definitely was up to 80 or 90
15 percent of the liver could be replaced by bone marrow
16 cells. And a paper by Don Orlic showing that if they
17 injected stem cells into the heart that was infarcted
18 that a significant amount of donor cells would be
19 found in the heart.
20 And in the data that I have shown you,
21 that we have up to 5 to 9 percent of the
22 differentiated tissue that seems to be derived from
23 the graft.
24 However, the majority of studies again
25 haven't really addressed the other question in
1 plasticity, meaning is it in vitro functional
3 And there is really only a single study
4 that has been able to show that, and it is again the
5 same study by Lagasse, et al., who showed that if you
6 did bone marrow transplantation in an animal that had
7 a failing liver, you could rescue the animal and take
8 it off the drugs that kept it alive.
9 Some studies have shown that there is
10 functional improvement, although the mechanism for the
11 functional improvement isn't completely known, and
12 that is to some extent similar to what you heard from
13 Dr. Gearhart.
14 And so there is a number of studies who
15 have injected cells in adults in organs and have
16 shown, for instance, that there was improvement in the
17 neuronal function, and that there was improvement in
18 heart function, although there is no proof that the
19 cells, per se, were actually responsible for doing
21 And the question will be is this
22 acceptable from a clinical standpoint, and if you show
23 only functional improvement without knowing the
24 mechanism for knowing why we see functional
25 improvement, and in the long term, again, that is not
1 a tenable situation, and we really have to dig into
2 this much further.
3 So what can adult stem cells be used for?
4 Well, I think like embryonic stem cells, or primordial
5 germ cells as you heard from Dr. Gearhart, the cells
6 are good tools to study five basic principles in
8 And we can study self-renewal, and we can
9 study differentiation and redifferentiation if that is
10 indeed the case, and learn what the implications for
11 that are.
12 And actually try to understand how organs
13 are being created, and what the genetic programs are
14 that you need to turn on. The cells, like other stem
15 cell populations, could be used for drug discovery,
16 for drug toxicity screening.
17 Adult stem cells could be used as systemic
18 therapies, and currently systemic therapies are done
19 with adult stem cells. Bone marrow transplantation is
20 done every day in many, many institutions around the
21 world, and so we can infuse these cells if we do not
22 think that they make tumors.
23 So since adult stem cells don't seem to
24 have that as their side effect, theoretically, we
25 could genetically correct cells for patients who have
1 deficiencies of certain enzymes. And the disease, and
2 Hurler's disease would be one example, and a second
3 possibility would be, for instance, in hemophilia,
4 where you need to have a cell that produces clotting
6 Or other congenital diseases, like Alpha-
7 1-Antitrypsin deficiency, or it could be used for
8 systemic cell therapy, which you would have to treat
9 in many, many different places in the human being.
10 For instance, muscular dystrophy.
11 So if you had a stem cell that was able to
12 engraft in most muscles, and you could genetically
13 correct it, you could correct that disease in patients
14 with that disease.
15 Systemic cell therapy may be more
16 complicated with cells that have the inherent
17 capability of making teratomas just because you would
18 always run the risk that teratomas might show up.
19 And then again if this field progresses
20 further, the same diseases that has been quoted for
21 embryonic stem cell therapies would also be on the
22 list here, and if indeed the cells can differentiate
23 into functional neuron cells, they could be used to
24 treat Parkinson's disease and many other ones.
1 And since the cells can appear to be able
2 to differentiate into functional liver cells, they
3 could be used either in vivo to replace the liver, but
4 also would be very useful to make bioartificial
5 livers, for instance.
6 We have shown, and others have shown, that
7 cells from bone marrow can contribute to new blood
8 vessels, and so this could be harnessed to create new
9 blood vessels in vivo, or actually the opposite; lower
10 these cells with anti-cancer agents, and actually use
11 them in a anti-angiogenesis approach for treatment of
12 cancer, and then many other diseases.
13 Again, we are not anywhere close to being
14 able to do this in any way, shape, or form, and a lot
15 of basic research still needs to go on.
16 So the first point that was on my previous slide, we
17 really need to spend a lot of time in trying to
18 understand what these cells are and aren't.
19 And at the same time, start thinking about
20 how we might be able to scale these up under GMP
21 conditions that conform with regulatory agencies, and
22 we will have to ask the question, as with any other
23 stem cell population, whether we will use the cells as
24 stem cells, or as more mature cells that have been
1 educated to some extent to become the final product
2 are totally mature cells.
3 And then again perform large scale culture
4 systems or develop large scale culture systems. And
5 then the last question is whether we should use these
6 cells in an autologous setting or in an allogeneic
8 Obviously adult stem cells for a number of
9 diseases could be used in an autologous setting.
10 However, if they were to be capable of repairing
11 hearts, and you have a heart infarct today, we would
12 not have adult stem cells sitting around instead of
13 your own to treat you at that moment in time.
14 So I think there are some issues, and Dr.
15 Gearhart also brought up the idea that with diabetes,
16 for instance, in Type-1, is an immune problem, and
17 again autologous transplantation may not be the way to
19 I think that for adult stem cells, the
20 initial trials may well be autologous, but that in the
21 long term, to make it more cost effective and more
22 available to many patients with certain frequent
23 diseases, that it might have to be an allogeneic
24 therapy, and then we are actually faced with the same
25 questions that investigators that work with ES cells,
1 and primordial germ cells are faced with. I think I
2 will stop there. Thank you.
4 DR. KASS: Thank you very much, Dr.
5 Verfaillie, for a clear, lucid, orderly presentation,
6 and it is very helpful to us. The floor is open for
7 questions, comments, discussion. Elizabeth Blackburn,
9 PROFESSOR BLACKBURN: Thank you. Could I
10 just ask a couple of quick clarifications. Dr.
11 Gearhart mentioned in response to Bill Hurlbut's
12 question the difference between fetally derived human
13 cells and mouse embryonic stem cells with respect to
14 their teratoma producing properties.
15 And I could not quite gather whether it is
16 human embryonic stem cells that are also known to have
17 any teratoma producing properties. Could you clarify
18 that for me, because you also had mentioned this, and
19 I wasn't sure if you were referring to the mouse
20 embryonic stem cell work or the human.
21 DR. VERFAILLIE: If you use either mouse
22 or human embryonic stem cells without
23 predifferentiating them into a committed progenitor
24 cell, and you use the stem cells as such, they will
25 form teratomas, because it is one of the tools that
1 investigators use that an embryonic stem cell has that
2 capability. So they will form teratomas.
3 PROFESSOR BLACKBURN: And then post-
5 DR. VERFAILLIE: I think there is very
6 little data on the human embryonic stem cells, post-
7 differentiation in vivo, and whether there is still
8 the tendency for these cells to make teratomas.
9 PROFESSOR BLACKBURN: And the second
10 question, since I promised that I would ask you about,
11 is the fusion issue, and which of course you have
12 raised in your talk as well, but again a question of
13 clarification for me, and maybe expanding on your
14 point that you said, well, fusions are going to be
16 I mean, the thing that immediately
17 occurred to me was that these fusions, as reported
18 from the in vitro culture, and I believe from
19 engraftment into mice, that they showed aneuploidy,
20 which of course anybody being a hallmark of tumor
22 So I wondered if those issues and perhaps
23 others were things you could tell us a bit more about
24 when you mentioned that you had concerns about the
1 DR. VERFAILLIE: Well, I think it is
2 something that because of the papers that were
3 published that elegantly showed that if you took a
4 somatic cell, an adult hematopoietic stem cell or
5 brain stem cell, and co-cultured it with embryonic
6 stem cells, and then put quite a bit of selectable
7 pressure on the system in the culture dish, they
8 proved that an embryonic stem cell quality could be
9 transferred to the blood brain stem cell.
10 And initially they interpreted this as
11 being reprogramming of the cell. But then it turned
12 out that there were four sets of chromosomes, and that
13 the cells fused.
14 And they took these fused cells and gave
15 them to -- injected them into a blastocyst as
16 hyperdiploid as cells with four sets of chromosomes.
17 One group was not able to create chimeric animals, and
18 the second group, under the direction of Dr. Austin
19 Smith, were able to create chimeras in the mice that
20 were what he calls unbalanced, meaning that he saw a
21 contribution to tissues, and that four sets of
22 chromosomes are actually tolerated.
23 For instance, the liver, where at least 50
24 percent of the cells, actually half, have two nuclei.
25 So I think that currently no investigator who has
1 worked with adult stem cells has set up the right
2 experiment to actually be able to disprove that it
3 isn't fusion.
4 I would argue that the data that I showed
5 today in vitro, where single cells make three layers
6 of the embryo, and these were euploid cells, meaning
7 that they had a normal set of chromosomes, and which
8 done in human, mouse, and rat, at the single cell
9 level, we can make the three major layers of the
11 So that would go against the argument that
12 at least in vitro, that all of it is caused by fusion.
13 In vivo, in our blastocyst experiments, 1 in 3 cells
14 could do it, which is much higher than the one in a
15 million cells that were quoted in the two papers that
16 were in Nature, but which indicated that one bone
17 marrow cell out of a million could actually make a
18 fused cell population.
19 And I think one in 50,000 neural stem
20 cells could actually cause fusion. So that was a very
21 rare event; whereas, our events are higher. We are in
22 the process of actually going back to these animals --
23 that we have cryopreserved, to try to identify that
24 since some of the transplants were done female into
25 male, we should be able to prove that we do not find
1 the y chromosome in the engrafted areas and in the
2 chimeric areas, which would get at the question
3 whether it is caused by fusion.
4 And so I think we really need to set up
5 experiments where we have generic markers on both
6 sides, meaning the donor and the recipient, so that we
7 can prove beyond any doubt that the in vivo results
8 would be the results from a fusion.
9 PROFESSOR BLACKBURN: Yes, I totally
10 agreement with that. I think the in vitro, and I am
11 very impressed by the in vitro results, and as you
12 said, there are questions in vivo.
13 I think in-part my question was addressing
14 this issue, and I was asking about the tumor forming
15 ability or otherwise, because it was not exactly 4N.
16 It was the median number of chromosomes was different
17 from simply 4N, suggesting that there was aneuploidy,
18 and for example, one might not find Y chromosomes, for
19 example, because those had been selectively lost.
20 So one would probably have to do much more
21 extensive genome-wide analysis of both of those to be
22 sure that there wasn't some genetic contribution from
23 the recipient cells.
24 But I certainly am very impressed as you
25 say with the in vitro results, and they seem quite
1 unequivocal, and I guess which is the question that
2 you are addressing, and we will find out as the in
3 vitro --
4 DR. VERFAILLIE: Yes, and I think we need
5 to set up the experiments where we have on multiple
6 chromosomes genetic markers. You know, sequences that
7 we can distinguish the donor and recipient between.
8 So these experiments need to be repeated.
9 DR. KASS: Questions? Janet Rowley,
11 DR. ROWLEY: Well, I would like to ask a
12 question that will include both Elizabeth, as well as
13 Catherine, because I was struck in the data that you
14 presented on your human cell lines that you had passed
15 for more than a hundred generations, that telomerase
16 was still active.
17 And I just am curious about that, because
18 many of us do believe that that is, if you will, the
19 internal clock that limits the number of doublings
20 that those particular cells can undergo.
21 And you derive these from adults,
22 presumably young adults in human, but at least adults,
23 and I am curious as to what you thought about the
24 mechanism of preserving the telomerase activity, and
25 maybe if Liz would have any further comments on that,
1 because again one of the critical features and
2 potential limitations of adult stem cells is the fact
3 that they would have potentially fewer doublings than
4 would those derived from embryos.
5 DR. KASS: Could I ask as a favor to the
6 non-scientists in the group if someone would just give
7 an ABCs on the telomerase matter, and just very, very
8 briefly, so that everybody can understand what the
9 discussion is about. Elizabeth, or Dr. Verfaillie, if
10 you could just give the barest --
11 PROFESSOR BLACKBURN: I am the worst
12 person, because I will fall into expert jargonese and
13 so I will try not to. So, telomerase keeps the DNA at
14 the ends of chromosomes replenished, and such
15 replenishment is necessary, because each time one of
16 our cells divides, the DNA at the end of the
17 chromosome is a little bit whittled away.
18 So, telomerase keeps putting back a little
19 extra DNA on to the ends of the chromosomes each time
20 on average a cell divides. So the issue that
21 Catherine pointed out in her talk was that if you
22 don't have telomerase after a number of cell
23 multiplications, that whittling away process would
24 have gone too far, and that sends a signal to cells to
25 cease dividing.
1 And so many, many normal cells in culture
2 are characterized by the inability to keep on
3 multiplying. Did that clarify the question? So many
4 cells do not keep multiplying because they turn the
5 cells’ telomerase off as part of their natural
6 differentiated state.
7 Cancer cells, on the other hand, have
8 telomerase, almost in a great majority of the cases,
9 and very up-regulated, and cells of the hematopoietic
10 system -- and I will defer to Catherine on this --
11 have an interesting intermediate situation, where they
12 have regulated telomerase activity that is turned on
13 in a natural and regulated way as the cells multiply
14 in response to signals in the body. Is that fair to
16 DR. ROWLEY: Yes.
17 PROFESSOR BLACKBURN: So I think it is a
18 very interesting question of why telomerases is turned
19 on in those cells that are multiplying so well in
20 culture, and has there been a selective event that has
21 allowed those cells, that for some reason have turned
22 their telomerases on in the culture conditions.
23 But those are the cells that are
24 outgrowing perhaps others in the population, and
25 perhaps that question might be answered by what is the
1 clonal efficiency with which you get these lines
2 growing out. You may already know this.
3 DR. ROWLEY: But can I intervene, because
4 you assured that it was often turned on, and maybe
5 these cells are identified because they never turned
6 telomerases off.
7 PROFESSOR BLACKBURN: Yes, and I don't
8 know if that is the typical situation when one puts
9 cells into culture, and I thought that they more often
10 would turn off and an earlier subset would keep
11 multiplying, and again I want you to correct me on
12 that cell growth phenomenon.
13 DR. KASS: Thank you.
14 DR. VERFAILLIE: So currently we do not
15 know whether it is often turned back on in culture.
16 If we look at the cultures, for the first 40
17 population doublings, the cells appear to grow
18 slightly faster.
19 And then a second wave of cells grows out
20 and it grows slightly slower. So initially we thought
21 that maybe the more classical senescing cells were
22 disappearing, and that those were the cells that were
23 growing faster, and the you then select for the cell
24 that has inherent -- you know, has the system turned
25 on to not be subject to the clock of aging.
1 The frequency with which we can grow out
2 the cells from human bone marrow is we believe one in
3 a million bone marrow cells. So it is a very rare
4 event, and so it will be quite difficult to actually
5 specifically ask whether it is turned on and then back
6 off, or turned off and then back on, unless we can
7 actually do some genetic trapping experiments to try
8 to ask the question.
9 PROFESSOR BLACKBURN: I'm thinking of
10 David Beaches' experiments in which he was able to
11 show that cells would spontaneously, if you keep them
12 in culture, turn their telomerases back on, because
13 that gives them some selective advantage.
14 DR. VERFAILLIE: Right.
15 PROFESSOR BLACKBURN: And so I was
16 wondering if such selected advantages occur in your
18 DR. VERFAILLIE: It could well be, and so
19 the culture conditions are very particular, and so I
20 didn't go into too much detail.
21 But if you do anything wrong to the
22 culture conditions, we cannot create the cell lines,
23 and so it might well be that it is what we call in my
24 lab a cultural artifact what we see, which would mean
25 that these cells may not exist really as such, but
1 actually are induced to become this long-term
2 proliferating cell by the culture conditions that we
3 put them under.
4 PROFESSOR BLACKBURN: Thank you.
5 DR. KASS: Janet, again, please.
6 DR. ROWLEY: I have two more questions.
7 One is a follow-up of a question that I asked you
8 about a year-and-a-half ago, on whether out of your
9 MAPC cells you can get hematopoietic tissue.
10 DR. VERFAILLIE: Well, I think I showed
11 you in vivo that if you infuse the cells into mice
12 that were either not irradiated or sub-irradiated,
13 that the cells appear to be able to differentiate into
14 hematopoietic elements that have red cell, and
15 granulocytic markers.
16 In vitro, we have had more difficulty to
17 try to do that, even though it appears now that we can
18 at least get for people who don't understand this, but
19 what would be yolk sac hematopoiesis, even though we
20 haven't really seen hematopoiesis that would occur in
21 the embryo proper.
22 But we can find cells that look like the
23 cells that have been created at the earlier stages of
24 development, where the initial one is made, which is
25 in the yolk sac.
1 DR. ROWLEY: And the other question is
2 more a more practical question. I don't know
3 precisely how many cells would be required to treat an
4 adult patient with a particular disease, and are the
5 number of cells required, or what kind of limitations,
6 using your system, would be faced if you have not one
7 patient, but hundreds or thousands of patients that
8 could benefit from a particular therapy?
9 Is this really going to be an applicable
11 DR. VERFAILLIE: I think it is a bit too
12 early currently to really be able to answer that
13 question. We have been able to take cell populations
14 and have them undergo 80 to a hundred population
15 doublings, which is really if you were able to do that
16 and not throw cells away along the way, it is 10 to
17 the 50th cells or something like that.
18 So it is an enormous number of cells that
19 you can in theory create. What I didn't go into too
20 much detail on is that the way that we have to grow
21 these cells is under very low density conditions,
22 meaning that the cells have to be far away from one
23 another, or otherwise they do not maintain their
24 undifferentiated state.
1 Which is quite different from embryonic
2 stem cells, which tend to grow in tight clusters.
3 From a bioengineering standpoint, meaning scaling it
4 up to making hundreds of millions of cells, will be a
5 major bioengineering question of how we can actually
6 adjust the system to be able to do that.
7 But on theoretical grounds, you know, if
8 you could overcome all the bioengineering problems,
9 you should be able to create enough cells to treat
10 multiple individuals, rather than a single individual
11 at a time.
12 DR. KASS: Question. Robert and then
14 PROFESSOR GEORGE: Just a very quick
15 question of clarification in response to Janet's first
16 point. On this question of whether they were --
17 whether the teleomerases were turned off and then
18 turned back on in the culture.
19 If it is not that, and if that's not what
20 is happening, the other possibility is that they were
21 never off to begin with?
22 DR. VERFAILLIE: Correct.
23 DR. KASS: Mike Gazzaniga.
24 DR. GAZZANIGA: Again, thank you for a
25 very excellent talk and a cautious talk I thought. I
1 thought it would be helpful for us to understand the
2 new pressures of a biologist like yourself, which are
3 the following.
4 Here you have this fantastically
5 interesting finding, and up until 5 or 10 years ago,
6 the normal way that such things would be treated is
7 you publish the work in peer review, and then you make
8 the stuff, whether it is reagents, or whether it is
9 cell lines available to others for reproducibility.
10 And that is a normal sequence of events
11 that we are all familiar with. And now we have the
12 bio-med inserting itself into these laboratories,
13 where all of a sudden it becomes proprietary goods
14 from this work.
15 When the original media picked up on your
16 story, and I guess it was The New Scientist, there was
17 this cryptic little paragraph in there about how they
18 had seen the patent on some of this work, which is a
19 very complete description, and how does that -- what
20 is going on here?
21 How can -- and this is where I would like
22 to go obviously, and obviously it is good for
23 everybody here to get these cell lines that you have
24 out to other labs, and reproducibility, and then the
25 process goes forward.
1 Are you constrained in some way, and has
2 life been made complicated because you didn't have
3 full public funding and you had to use this other
4 money, or was that your own? What is going on?
5 DR. VERFAILLIE: So the work was really
6 done at the university with NIH funds and university
7 funds, and so there was really no private funds,
8 except for the small amount from the company that was
9 listed in the beginning, has gone into the work that
10 we have done.
11 And because of the possible importance of
12 the observation, the university, as well as myself,
13 thought we should get some kind of protection, even
14 though I am not sure that you can truly patent stem
15 cells, because all of us have them.
16 But just such that we would be in a
17 position to work with biotech companies to be able to
18 produce large-scale numbers of cells and things like
19 that, which is hard to be funded to known private
21 So there is patents pending on the cell
22 population. Currently, that really has not precluded
23 us of collaborating with other institutions, or
24 investigators within the same institution.
1 So they have collaborations with 10 or 15
2 different groups within the U.S., or outside of the
3 U.S., depending upon the expertise that we need, to
4 try to recreate the cells in other laboratories, and
5 actually use their expertise, since I am a
6 hematologist, and not a liver physician or a neuro
8 And to actually be able to use expertise
9 in other people's laboratories to move the research
10 forward. So there are some minimal ties attached to
11 working with the cells, but I think it isn't
12 overcomeable, and it really has not been an issue with
13 other academic investigators to collaborate with them.
14 And teaching people from those labs to
15 come and to grow the cells, and at least start working
16 with the cells. But it is a very complicated and it
17 is a -- and I have had myself a lot of problems in
18 trying to find the right patent between potential
19 biotech interests and academic interests.
20 DR. GAZZANIGA: Right, and you are not
21 alone in that dilemma. So are there other MPAC lines
22 at other institutions now that behave like yours, or
23 is yours still the Golden Grail here?
24 DR. VERFAILLIE: We have given out the
25 mouse, and to some extent, human MAPC lines to other
1 investigators who are now setting the lines back up.
2 We are also explaining and teaching people how to
3 create them from beginning bone marrow.
4 And I know that there is one group in
5 Japan who I think pretty much as the system set back
6 up from human bone marrow. You know, they still need
7 to do some additional studies to prove that it is
8 really MAPCs, but we trained a person from there for 3
9 or 4 months in my lab, and they went back to Japan,
10 and were able to it appears to recreate them.
11 DR. KASS: Could I ask a couple of sort of
12 semi-scientific and semi-practical questions? How
13 hard is it -- I mean, you have just indicated that not
14 many people have already been able to do this, but how
15 hard is it to find these cells?
16 And by which I mean two pieces, and in how
17 many individuals in which you look for them can you
18 find them? And how hard is it to find -- how rare are
19 they, and how hard is it to find in any particular
21 Both of these questions bear upon at least
22 a preliminary assessment of how useful this might be
23 clinically speaking down the road, although things
24 could change where you might be able to enhance the
1 But could you give us a preliminary sense
2 of this?
3 DR. VERFAILLIE: I think we have studied
4 now between 70 and 80 normal humans to try to identify
5 the cells. The age range, the youngest donor was two,
6 and the oldest donor was 55. The majority are young
7 adults who want some money to donate bone marrow at
8 the universities.
9 DR. KASS: The two-year old?
10 DR. VERFAILLIE: No, the 20 year olds.
11 The 2 year old actually did a bone marrow donation for
12 a sibling who needed a bone marrow transplantation.
13 So we have been able to create the cells I would say
14 in about 70 percent of the individuals that we have
15 looked at.
16 Whether that means that the other 30
17 percent didn't have it, or there was some technical
18 issue that came about, and we were not able to create
19 them, we start out with 10 milliliters of bone marrow,
20 and we would usually find a few clones that can
21 actually grow out.
22 And so really the frequency is quite low,
23 and it is one in a million, and that is at least the
24 estimate that we have right now. But there is lots of
1 bone marrow and so one in a million isn't an
2 impossible task to do it.
3 DR. KASS: And could I also follow up on
4 the question of these cells and their promise,
5 assuming the best, and the embryonic stem cells,
6 assuming their best.
7 This is not a question of whether one
8 should prefer one line of research or another, or
9 whether we should now go ahead with them. But is
10 there anything specific that you could imagine could
11 not be done therapeutically with these MAPC cells that
12 you would then need cells derived from embryonic
13 tissue to do?
14 Or is this in the rosiest division, is
15 this really a substitute, and one that might even have
16 the rejection problem solved if I am dreaming?
17 And this is not a question about whether the other
18 research should go forward, but really what is the
19 best promise of this research so that at least we can
20 think about it?
21 DR. VERFAILLIE: Well, I think that the
22 data that we have in vitro suggests that we can create
23 cells of the three germ layers of the embryo, and so
24 theoretically, you could envision that you might be
25 able to make more than we have done so far.
1 We have made liver-like cells, and brain-
2 like cells, and epithelial cells, and we have not
3 tried all the other ones. In vivo, the blastocyst
4 experiment, unless that is a fusion event, and if it
5 isn't a fusion event, would indicate that the cells
6 hold the inherent promise of making all the different
7 cell types that make up the tissues, the somatic
8 tissues of an animal.
9 So again that would suggest that is under
10 -- that if we changed culture conditions further that
11 we might be able to, for instance, create insulin-
12 producing beta cells, which we haven't done, or create
13 two heart muscle cells that function like heart muscle
14 cells, and don't just look like it.
15 So if all these promises hold true, and if
16 we continue the cultures and they can be expanded even
17 further into 80 or 90 population doublings, and so
18 there are lots of ifs here, they may be able to be
19 used to treat a large number of diseases.
20 The problem at this point in time is that
21 there is so many ifs that it is a very difficult
22 question to specifically answer.
23 DR. KASS: Of course, and I appreciate
24 that, and on the question of the longlivedness, or the
1 half-life of these things, you have gone through -- in
2 vitro is what? It is what?
3 DR. VERFAILLIE: From 80 to 100 population
5 DR. KASS: And it is obviously too early
6 to say how much longer, and whether those conditions
7 are matched in vivo. But when the people say that the
8 promise in terms of longevity for cells derived from
9 the adults is really much less, is there anything to
10 be said on that question of the basis of knowledge now
12 DR. VERFAILLIE: Human embryonic stem
13 cells have been kept in culture now for 350 or 400
14 population doublings. So that is 3 or 4 times as long
15 as the adult cells. So we are striving to go there,
16 but we just need time to do that.
17 Are these cells going to be able to do
18 that? As far as we can tell, after 80 population
19 doublings, there is no shortening of telomeres, and so
20 that means that there is at least another 50 or 60
22 If for some reason telomerase is shut off
23 along the way for reasons that we currently don't know
24 why that might be, then the longevity would be less
25 than what has been shown for embryonic stem cells.
1 Now, for classical adult stem cells, if
2 you take hematopoietic stem cells that make blood, but
3 not something else, they would not go for 80
4 population doublings.
5 So there is something special about these
6 cells, that they can overcome this senescent block at
7 60 or 70 population doublings, which is actually long
8 for any other adult stem cell.
9 DR. KASS: Thank you very much. Questions
10 or comments? Janet again, please.
11 DR. ROWLEY: Coming back again to partly
12 the real world in this iffy situation, and it is a
13 question of the practicality for treatment for
14 particular individuals.
15 It seems to me that the notion that you
16 might be able to derive these MAPC cells from an
17 individual who had some medical problem might have
18 some limitations because it probably takes 3 to 6
19 months, or so to get enough cells to then be able to
20 use them therapeutically in that individual, and that
21 is always assuming that the individual has some kind
22 of a somatic disease, and not the basic underlying
23 genetic problem.
24 So then the way to get around that if it
25 really is 3 to 6 months, and you don't have that
1 window of time, would be to do somatic cell nuclear
2 transplant. Now, have you ever tried that in your
3 MAPC cells?
4 DR. VERFAILLIE: In collaboration with Dr.
5 Jaenisch, and two weeks from now we will try the mouse
6 MAPC cells in mouse eggs, and ask whether the
7 efficiency of nuclear transfer would be closer to what
8 you would see with embryonic stem cells, and where the
9 efficiency is much, much, much higher than if you use
10 a classical adult cell.
11 And that might improve efficiency of
12 making cloned embryonic stem cells.
13 DR. ROWLEY: But I am thinking of the
14 other experiment. You have a patient who is
15 desperately ill, and so you would have cells from that
16 patient, and you would want to use the nucleus of the
17 patient's cells into your MAPC cells, and so that is a
18 different thing.
19 You have got these cell lines, and how can
20 you make them more compatible with the patient, and
21 agreeing that you can't get rid of the mitochondrial
22 problem unless you do additional manipulations and
1 But have you ever tried to replace the
2 nucleus in your MAPC cell with a nucleus from an adult
3 somatic cell?
4 DR. VERFAILLIE: No, we have not yet.
5 DR. ROWLEY: Do you plan to?
6 DR. VERFAILLIE: We might.
7 DR. KASS: We could always get everyone at
8 the age of 15 to put away a little bit of marrow for
9 the time that we might need it.
10 DR. ROWLEY: Another reason to save cord
12 DR. KASS: This is your chance, council
13 members. This is a wonderful opportunity. Questions?
14 DR. ROWLEY: Well, I would just be
15 interested from Catherine's point of view on her
16 answers to some of the questions, to the two questions
17 that I posed at the end to John Gearhart, and again
18 give her the option to do this as a written response
19 rather than a direct response, but I think it may be
20 easier to -- and the second question, which may be
21 very simple to answer in terms of the kinds of
22 restrictions that you find now in funding.
23 And I would assume since you are dealing
24 with adult cells that there aren't any, but I would be
1 interested in your perspective on the funding, in both
2 government and other agencies.
3 DR. VERFAILLIE: Well, currently for the
4 work that is ongoing in my group, which works with
5 adult stem cells, actually the amount of funding that
6 has become available through the NIH has increased
7 dramatically over the last few years to support this
8 kind of research.
9 So that has not been a problem. I have
10 wanted to compare these cells carefully with embryonic
11 stem cells, and so we are in a position currently to
12 do this in a mouse, but mice aren't humans.
13 And so we have really not been able to do
14 that until earlier this year when human embryonic stem
15 cell research was allowed in academic institutions
16 under NIH funding.
17 And as I mentioned, we had actually gone
18 out and tried to recruit an investigator with that
19 kind of expertise to be in a position to try to
20 address some of the questions that have come up here,
21 and are these cells going to be equipotent.
22 And I think to date, even though they are
23 exciting and they seem to be quite potent, I can't
24 really say whether that is the case. And so
25 ultimately we won't be able to answer this question
1 until we can truly compare them and not across country
2 borders, but actually within the same institution,
3 where people can look at the two cell populations at
4 the same time.
5 And so in that respect, I think that the
6 lack of funding for embryonic stem cell research in
7 humans has made it impossible up until just recently
8 to be able to do that.
9 DR. KASS: Michael Sandel.
10 PROFESSOR SANDEL: I wonder if I could put
11 to you the same question I put to the previous
12 speaker. Given that some people regard embryonic stem
13 cell research as morally problematic, what would you
14 think of the idea of imposing a moratorium on
15 embryonic stem cell research until we could assess
16 what might be achieved by adult stem cell research?
17 DR. VERFAILLIE: I think that my answer is
18 very much in line with what you heard from Dr.
19 Gearhart. I think that the main reason why we -- to
20 investigate in the field of embryonic stem cell --
21 human embryonic stem cell research is to be able to
22 compare and contrast the two cell populations at the
23 same time.
24 I also think that what we did in our
25 culture dishes to try to differentiate these MAPCs
1 into liver-like cells or neuronal-like cells is really
2 based on what has been learned from mainly the mouse
3 embryonic stem cell field, where investigators have
4 been able to take these cells and drive them in vitro
5 to become certain cell types, even though that is not
6 a hundred percent fool-proof, and it is not completely
7 figured out how you should do that.
8 So I think if you have a number of
9 different cell populations at the same time, we try to
10 test all these different questions. What we learned
11 in adult cells might be applicable to embryonic stem
12 cells if they are the cells that ultimately will be
13 the suitable source for our clinical applications or
14 the other way around.
15 And so I think stopping research in one
16 field actually will slow down research in the other
17 field, and it would be either way. In other words, if
18 you stop our research in adult cells, or embryonic
19 stems, as I think what can be learned in the two
20 systems should be translatable in the other system.
21 And so I think if you were to ban all
22 embryonic stem cell research, it would really slow
23 down the insight that could be gained in adult stem
24 cell research.
25 DR. KASS: Rebecca Dresser.
1 PROFESSOR DRESSER: This is unfair, but I
2 am wondering if you had any ideas about the cost of
3 such a procedure? I mean, just based on what you have
4 done in mice, and you mentioned at the very end that
5 to be cost effective that you would probably would
6 have to just have a number of cell lines and not rely
7 on the patient cell.
8 Is this going to be a very, very expensive
9 technology, and where we have to worry about -- well,
10 if all these ifs work out, will we have to worry about
11 who has access, or will it be comparable to the stem
12 cell transplants that we do now with bone marrow now?
13 Or what do you think?
14 DR. VERFAILLIE: Well, I think it will be
15 relatively expensive if you do it on a single person
16 basis, and you will have to create the cell lines from
17 the beginning, rather than go going to a frozen stock
18 of cells, where you have a very well-qualified product
19 to start with and where you expand cells.
20 And so you might even have already
21 committed cells frozen as well, and so the cost to get
22 to that point would have to be incurred once rather
23 than doing this over, and over, and over again.
24 The costs I think -- well, it is hard to
25 say, because I am not sure how much of the regulatory
1 issues we have actually complied by at this point in
2 time to actually truly gauge how much it would cost.
3 But I think that by the time that you do
4 all the quality control tests for infectious agents
5 and things like that, that amounts to quite a bit of
6 money for each cell line that you try to establish.
7 And in the long term I think it would
8 probably be more cost effective if you would have a
9 therapy for heart infarcts that you could go to a
10 limited number of cell lines. And to put numbers of
11 them, I don't really know.
12 It would probably be in the range of a
13 bone marrow transplantation currently, which is quite
14 expensive. So it is anywhere between $50,000 and
15 $200,000 per patient.
16 If you had qualified cells that were
17 frozen, and then you could expand them for a short
18 period of time and do a limited number of tests at the
19 end, the amount of cost incurred would really be all
20 up-front, and then there would be a relatively small
21 amount per patient.
22 PROFESSOR DRESSER: I guess the other
23 thing is that bone marrow transplants work fairly well
24 with some illnesses and not with others, and would you
1 expect to see those kinds of results with these kinds
2 of therapies?
3 DR. VERFAILLIE: I think that would highly
4 depend on the type of disease that you tried to treat.
5 You know, you are all well aware of the treatments
6 that have been used for Parkinson's disease, which the
7 trials that were done in Sweden have made little
9 But when this was extended in multiple
10 hospitals in the West, there were a lot more
11 complications if it was done on a larger scale. So I
12 think that depending on the disease that you go after
13 that it may work better or worse, and it is really way
14 to early to be able to comment on that.
15 DR. KASS: Bill, do you have a question?
16 DR. HURLBUT: Well, if we have time, I
17 would like to ask a couple of scientific questions if
18 that is all right.
19 DR. KASS: Please.
20 DR. HURLBUT: Do I understand this
21 correctly that you are saying that your MAPC is put
22 into the blastocyst to perform more cell lines than do
23 other adult stem cells?
24 I thought that adult stem cells generally
25 formed lines in a blastocyst?
1 DR. VERFAILLIE: There are 3 or 4 papers
2 published on adult stem cells into blastocyst
3 experiments. There is one paper published by a German
4 group, where they took purified hematopoietic stem
5 cells, and injected them into the blastocyst, and what
6 they were able to show was that the cells gave rise to
7 some hematopoietic elements, and that they actually
8 recapitulated the developmental behavior of
9 hemoglobins, which switched at different stages of
10 development during embryos, fetuses, and then adults.
11 They did not see any contribution outside
12 of the hematopoietic system. The second paper is a
13 paper from a Swedish group, where they had taken
14 neural stem cells that have been cultured, and
15 introduced them in the blastocyst, and as far as I
16 know, they have never had animals been born alive.
17 And they saw a contribution to a few
18 tissues, but not all tissues of the mouse fetus. And
19 in the last papers, we did a paper by Austin Smith,
20 the one that reported on fusion, where they had taken
21 defused cells and given them to a blastocyst again,
22 and it showed a contribution in one animal that was
23 born, and that was really only a single animal, to the
24 liver and a few other tissues.
1 But it was not quite the amount of
2 contribution that I showed in the picture here, where
3 every single tissue of the mouse appeared to be having
4 a fraction of the single MAPC cell.
5 DR. HURLBUT: That is very, very exciting.
6 Another question that I think might be of good general
7 interest to our council, but he question of whether
8 transdifferentiation is occurring, or even the process
9 of embryonic stem cells just differentiating, it is
10 always clouded by the question of how do you know when
11 there is actual differentiation taking place?
12 In other words, just because you follow
13 one or two gene expressions, you don't know, and one
14 of the problems with embryonic stem cell therapies
15 will be to get the target tissues up to speed, like
16 beta cells producing enough insulin.
17 I know that there are advances being made
18 on this, but can you just give us a general
19 description of how you identify when you are satisfied
20 that a tissue has in fact been produced?
21 And maybe tell us a little bit about the -
22 - maybe we need a little education on messenger RNA
24 DR. VERFAILLIE: Okay. The criteria to
25 say that you produced tissue I think needs to include
1 that you turned on the genetic program that is
2 compatible with the tissue that you want to produce.
3 You find therefore proteins from the
4 genetic program in the cells, and the cells have
5 morphological changes consistent with the cells that
6 you are looking for, and the cells have functional
7 characteristics of the tissue that you are looking
9 So what happens in a cell is that in an
10 undifferentiated state a number of gene programs are
11 shut down, meaning there is no transcription to the
12 messenger RNA, and you will find no protein, and
13 therefore no function.
14 During a differentiation process, you come
15 in with a growth factor or a cytokine, or a stimulus
16 from the outside, and you trigger a certain set of
17 signals that then open up a new genetic program and
18 the first thing that happens is that you transcribe
19 messenger RNA, that then gets translated into proteins
20 and/or sugars, that then supposedly give a new
21 function to the cell.
22 So what we have been looking for in vitro,
23 and that is where most of our work has been done
24 initially, is actually taking an undifferentiated cell
25 and showing that a certain genetic program isn't
1 turned on, meaning that you don't find mRNA, and you
2 don't find protein, and you don't find function.
3 We then switch the culture conditions and
4 add triggers by trial and error, to a large extent to
5 try to activate certain genetic programs. And if we
6 do that, we look for protein and mRNA first.
7 So we look to prove that the genes are
8 turned on, and then we look to prove that these gene
9 products actually give rise to proteins. We have gone
10 to the next step also and actually tried to then take
11 the cells that we believe that are like brain or like
12 liver, and started asking questions.
13 If it is a liver cell, it should secrete
14 certain things. It should have the machinery to
15 detoxify blood and things like that. So we have been
16 able to show that in the liver lineage, for instance,
17 that we do turn on the programs to make albumin, which
18 is one of the major proteins that is being secreted in
19 the liver and is present in the blood.
20 These cells have, for instance, cytochrome
21 p450, which is a massive machinery in the liver that
22 helps detoxify the blood components. And we can show
23 that it is there, and it responds in the correct ways
24 as liver cells would do.
1 So that is what you do in vitro, and in
2 vivo, it is a bit more complicated, and you really
3 need to use animal models where there is a disease.
4 So you would have to show that the cells ingraft and
5 you can find the donor cells.
6 You would have to show that they turn on
7 RNA and protein, and therefore have this genetic
8 program turned on. And then function, which means
9 that if you take an animal that has a failing liver,
10 and you give the liver cells to this animal, the
11 animal will now live without having drugs that keeps
12 it alive.
13 And so that would prove that the cells
14 that you put in have actually acquired the ability to
15 function like a liver cell. And so for adult stem
16 cell research, very little proof of the latter is
17 actually present.
18 For embryonic stem cell research in mice,
19 there is a lot of evidence, and in the human embryonic
20 stem cells, that evidence is just starting to become
21 available, just like it is with adult stem cells.
22 DR. HURLBUT: Could I ask one last little
23 question? How many genes are we talking about here;
24 like hundreds, or thousands, and how many do you
25 monitor in fact?
1 DR. VERFAILLIE: Well, we usually monitor
2 between -- well, there is probably hundreds of
3 thousands that get turned on, and so using the new
4 technologies, the array technology, and the proteomics
5 technology, that is one of the things that we are
6 looking at, because it will give us a much better
7 insight in the whole programs that are being turned
9 We just pick and choose the ones that we
10 think are known to be important at certain stages of
11 the differentiation. So, for instance, if you go from
12 a stem cell to a liver cell, we know that you have to
13 turn on X number of genes that happen to be known to
14 be turned on.
15 So we look at 2 or 3 that are early, and 2
16 or 3 that are in the middle, and then 5 or 6 at the
17 end. We have not exhaustively looked at all of them
19 But I think with the human genome being
20 sequenced, we now have the tools in hand to now take
21 cells created from stem cells and look at the whole
22 program of genes that is present, and what we created
23 in a culture dish, compared to what is actually
24 present in real life in vivo, and get a feel of how
25 closely we actually are getting to the real cell.
1 DR. HURLBUT: Thank you.
2 DR. KASS: Could I -- Robby, did you have
3 a question? Why don't you go first, because I have a
4 couple of things as well. Please.
5 PROFESSOR GEORGE: Actually, I just wanted
6 to follow up the question that Dr. Kass asked earlier
7 just for clarification, and I recognize that there is
8 a great deal of uncertainty as to what the future
9 holds in your area for research, as well as in
10 embryonic stem cell research.
11 And estimating or evaluating what the
12 prospects are therapeutically is a speculative
13 business, but having all of that in mind -- and I was
14 not clear in responding to Dr. Kass whether you
15 identified some areas in which knowing what we do know
16 now about the differences between embryonic stem cells
17 and the MAPC cells, it is possible to identify some
18 areas where we just know that whatever the prospects
19 are for MAPC cells that they won't be able to do, or
20 our therapies won't be able to be developed based on
21 them to do certain things.
22 And that there is at least a prospect of
23 embryonic stem cells being used to do.
24 DR. VERFAILLIE: It is so very hard for me
25 to answer that question, just because embryonic stem
1 cells have been worked with for so much longer, and so
2 investigators have been able to, for instance, make
3 cells that secrete insulin to some extent on demand,
4 which has not been accomplished with adult stem cells.
5 There is a little bit of evidence from
6 pancreatic tissue itself that there might be
7 precursors that can do that, but from MAPCs, for
8 instance, we have not been able to do this yet.
9 It doesn't mean that we can't. I don't
10 know that answer. So there is a lot more experience
11 with embryonic stem cells and there is a lot more --
12 at least in the mouse system, there is a lot more
13 known on how to try to trigger certain differentiation
14 programs and whether the MAPCs will respond to the
15 same extent and to the same degree.
16 And I think that currently I can't really
17 answer that question.
18 PROFESSOR GEORGE: But asking if you look
19 at it and not asking what do we know MAPC cells will
20 be able to enable us to do, and have a prospect of
21 doing, that embryonic stem cells have a prospect of
23 But if we simply ask the question as do we
24 know just on the basis of the facts of what we know
25 about the differences, and that there are in fact some
1 things that MAPC cells, no matter what, won't be able
2 to do. Or is the answer that we just don't know?
3 DR. VERFAILLIE: I think we don't know
4 currently, and I can't really answer that question,
5 because we just don't know at this point in time.
6 DR. FOSTER: I just want to interrupt with
7 this one point. Those questions are really hard to
8 answer, but there is another whole area that is going
9 to impact what you are going to use cellular based
10 therapy for.
11 And that has to do with good vectors,
12 retroviral gene therapy, and that you are going to
13 accomplish with other diseases that you don't have to
14 use cells for at all.
15 I mean, the most recent thing in severe
16 combined immunodeficiencies in humans, is you put a
17 retrovirus in, and you put the common gamma chain in
18 for about five cytokines, you know, for these kids.
19 It was just in the New England Journal a couple of
20 weeks ago, or three weeks ago, or something like that.
21 And they are now two years out, and so
22 there are going to be a whole lot of diseases that you
23 are not going to have to use regenerative therapy or
24 cell therapy. You can't predict those things either
25 at this point.
1 So I think if you try to jump way ahead of
2 what the basic science is doing, then you are prone to
3 error, and I know everybody wants to know whether an
4 adult cell is better than an embryonic stem cell, or
5 something like that.
6 And I don't think you can answer those
7 questions, and one of the things that we have heard
8 from both the investigators this morning is that they
9 cross-fertilized with each other.
10 And so -- I mean, that you could not have
11 done what you are doing in the adult cells without
12 what had already been done with the embryonic cells.
13 So I just would argue against trying to
14 push investigators to say whether an adult stem cell
15 can do this or do that at this point, because we have
16 not even taken into consideration many other
17 approaches to human disease.
18 I don't mean to be fussy, but I do think
19 that that is an important thing.
20 PROFESSOR GEORGE: But I was actually
21 asking -- well, I think the question I asked was that
22 it really is about what we know now. The question is
23 do we know now that there are certain differences,
24 that as a result of which the prospects for the one
1 area are different from the prospects of the other.
2 And I got my answer. Thank you.
3 DR. KASS: Let me take the privilege of
4 the Chair to expand in a way Dan Foster's comment in a
5 direction that he might not have intended.
6 DR. FOSTER: That does not surprise me.
7 DR. KASS: Well, I mean, you are a genial
8 sort, and I think you won't -- I mean, one of the
9 things that one has to remember in this conversation
10 is that wonderful as the stem cell approach is from
11 whatever source to the treatment of these diseases,
12 that is not the whole area here also.
13 And that the gene therapy is not the whole
14 story as well, and there are preventive measures, and
15 there are all kinds of other things. I mean, the
16 conversation, because we are taking it up, gives it a
17 certain type of dramatic focus and concentration.
18 But for the people who work in clinical
19 medicine, they know that this is -- that there are
20 lots of ways to try to skin this cat. But I wanted to
21 ask a couple of -- to make a comment, and then ask a
22 couple of questions.
23 You have talked understandably and very
24 welcomely to us about your own very exciting work.
1 There is a great deal of skepticism about many of the
2 published works in using adult stem cells.
3 And unfortunately, for better and for
4 worse, these reports are caught up in the political
5 controversy that now surrounds us, with people on both
6 sides having a stake in either making the results on
7 one line of work seem better than the other, precisely
8 because they are wed to an either/or choice.
9 Can you, abstracting from all the
10 political considerations, and the various axes that
11 various people are grinding on these poor cells, can
12 you say anything at all generally about the kinds of
13 initial reports of a clinical sort that we have had
14 with alleged adult stem cells?
15 Because at least according to some
16 accounts, these have been very exciting, and yet there
17 is a great deal of skepticism about whether these are
18 in fact stem cells that are producing the results.
19 Can you tell the council anything at all
20 about how we should at the moment regard the news that
21 is coming out to us in this area? How should we
22 receive it?
23 DR. VERFAILLIE: There have been several
24 publications that came out over the last 1 or 2 years
25 now, where investigators or clinicians have looked at
1 individuals who were transplanted with classical bone
2 marrow transplantations, and looked in tissues outside
3 of the hematopoietic system to ask whether bone marrow
4 derived of donor-derived cells could be found in
5 different tissues.
6 And the reports that have come out have
7 indicated fairly significant levels of contribution to
8 certain tissues, meaning they have found cells in the
9 heart, and they have found cells in skin, gut, liver,
10 and so forth.
11 And we really have not looked in the same
12 situation to see whether we can confirm these data or
13 not. I know that some clinical groups have put in
14 doubt to some extent the degree of contribution that
15 has been reported, and it is not quite clear whether
16 the 5, 10, or 20 percent that has been quoted in some
17 papers is indeed actually going to hold up over time.
18 I think there is some contribution, and
19 the question in my mind still is how clinically
20 important is it what investigators have seen or what
21 clinicians have seen currently.
22 If you go strictly by the term of stem
23 cell plasticity, none of these studies really show
24 that it was a single cell, or it was a blood cell that
1 gave rise to these tissues, and it might still be that
2 some contaminating cells were contributing to that.
3 And really none of these studies have
4 shown that this has had any clinical impact on what
5 was going on in these patients. And so they didn't
6 really show that you restored function of the organ
7 that the cells were found in.
8 DR. KASS: I was thinking of a recent
9 report on the Parkinson's cases.
10 DR. VERFAILLIE: Correct. So the
11 Parkinson's cases were -- and that is with fetal brain
12 tissues, and are those the reports that you are
13 referring to?
14 DR. KASS: Yes.
15 DR. VERFAILLIE: And so there has been a
16 series of patients transplanted in Sweden with
17 Parkinson's disease, where one team of investigators
18 in a non-controlled study, shows that implantation of
19 the fetal tissue brain -- fetal brain tissue into the
20 brain of patients with Parkinson's disease could
21 rescue patients, and could actually correct the
23 And actually have now done so for some
24 patients for more than 10 years. Now, these were
1 highly selected patients, and done by a single group
2 of investigators.
3 The same was done in the west in 3 or 4
4 institutions, and some patients got better and some
5 patients did not get better. But I think that gets to
6 the proof of concept that if you have the right cells,
7 and if you can create the right cells, and if it is
8 from embryonic stem cells, or adult stem cells, or
9 from tissues itself, that there might be a way of
10 correcting Parkinson's disease.
11 But there is again -- and I think it would
12 behoove us to really look carefully at exactly what
13 single cell or fused cells that we have to put into
14 the brains of patients with Parkinson's disease to try
15 to correct the disease, and not over correct it as it
16 was done in some of the patients in the U.S., where
17 they had more side effects from the therapy than they
18 initially had from their Parkinson's disease.
19 And so even though there is an enormous
20 amount of pressure on all of us with stem cell
21 research to try to come up with therapies yesterday, I
22 have been very, very cautious in telling people that
23 do the clinical work that you can't just go around and
24 take stem cells and put them in places in the hope
25 that they will work.
1 Because we will get into situations like
2 the gene therapy field, where a couple of awful
3 problems have popped up, and have actually halted the
4 clinical potential of these cells enormously.
5 DR. KASS: Could I follow that up, because
6 if there had been more time, I would have asked Dr.
7 Gearhart this question as well, and you are a
8 clinician who deals with patients that are also -- now
9 thanks to your new results, and I am sure that you are
10 getting lots of calls as well.
11 There is an ethical dimension to this area
12 that worries not so much about where you get the cells
13 from, but how we deal with the desperately sick
14 patients looking for any sort of hope.
15 And let me say flat out that in-part to
16 fend off the opponents, the people in the scientific
17 community and medical community, has to some extent
18 not been adverse to shall I say hyping the benefits
19 here and possibly even taking rather cruel advantage
20 of these hopes.
21 And from what I hear from you, and from
22 what I hear from Dr. Gearhart, these therapies, there
23 are lots of problems to be solved before these things
24 will be made available.
1 And that is not to say that there isn't
2 this enormous promise, but what can you tell us, or
3 what advice would you give us about we could
4 responsibly speak about this promise without behaving,
5 let me say, unethically in dealing with the very
6 patients who are coming to us for help?
7 And I think that's something that you have
8 probably faced directly, and whatever help you could
9 give us on that would be welcome.
10 DR. VERFAILLIE: Well, like Dr. Gearhart,
11 my e-mail and phone have a lot of messages on them
12 from patients locally, around the country, and around
13 the world who want to bring a child or a parent with a
14 certain disease, and want us to treat whatever disease
15 you can come up with.
16 And we have to speak the truth, and even
17 though we are excited about the work that we have, and
18 for the work that people do in embryonic stem cells,
19 at this point it is a promise, and I don't think there
20 is any data to say that in the next 1 or 2 years we
21 will actually be in clinical trials with any of this.
22 So we really have to tell patients,
23 families, and whomever, that currently we are trying
24 to cure mice, but a lot of mice have been cured with a
1 lot of different things, and that doesn't necessarily
2 mean that it will translate into humans.
3 And so we need to do the regular science
4 that needs to be done to come up with a therapy that
5 is both potentially useful and for certain not
7 And so that the last part of that whole
8 thing is really where everything sits. And so we
9 could go ahead and do things now, but then run into
10 major, major complication issues which would make
11 patients way worse off than they started out.
12 You could argue that bone marrow
13 transplantation, there was not a whole lot known when
14 the first bone marrow transplants were done, and that
15 is before I started in bone marrow transplantation,
16 and probably some patients didn't fare that well
17 either in the beginning.
18 But people ultimately still have to learn
19 by doing it in humans, but we have to learn as much as
20 we can in culture dishes, mice, rats, and larger
21 animals before we proceed with therapies for things
22 that are not immediately legal.
23 And so it is not because you are diagnosed
24 with Parkinson's today that four months from now that
25 you will die from your disease, which is different if
1 you have a acute leukemia, where there is really no
2 other solutions.
3 And so I also think it will have to be
4 graded depending on the type of disease that you start
6 DR. KASS: And I have one last question,
7 and I don't think we will have another opportunity in
8 this discussion, but this comes to Rebecca Dresser's
9 question about the costs, and how to think about this.
10 And also about the applicability.
11 There was recently a meeting of the major
12 biotech companies in Princeton, and our scientific
13 director, Dick Roblin, was there, and they were
14 discussing among other things the question of the
15 solution of the immune rejection problem from all
16 these various things.
17 And all of the ones that were present
18 there are putting their research money not into
19 somatic cell nuclear transfer to deal with the
20 rejection problem, but into other means, for a reason
21 that would have never have occurred to me until it
22 came back from this meeting, which is to say that if
23 you have highly individualized treatments, case by
24 case, that at least under present regulatory systems,
25 if you call these things products, each one of them
1 has to be approved independently by the FDA before it
2 can be used.
3 And so the question is whether or not --
4 and in partly thinking about the cost and the
5 scalability, and the things that might make things
6 universally applicable, doesn't it make sense more to
7 be thinking more in terms of cell lines, whether
8 embryonic or adult, and that could be made universally
9 applicable, rather than trying to continue to think
10 each person, his or her own replacement, given these
11 practical problems of scale and product approval?
12 I am not sure that the question was
13 clearly put, but it bears upon the efficacy of this in
14 terms of long term clinical use, and the questions of
16 DR. VERFAILLIE: Ideally, it would be
17 personalized therapy, and so you would create cells
18 that are completely compatible with the person that
19 you need to treat, except again in situations where
20 there is an autoimmunity issue, which makes it
22 And if it is an autoimmune problem
23 starting out, then cell therapy is probably not the
24 best way to go about doing this. For instance, Type-1
1 diabetes would come to mind, where there is really a
2 rejection of your own islet cells.
3 I think the costs -- and I spoke to that
4 just a little bit before -- of creating everybody's
5 own cell line will in the long term will be extremely
6 high, and it will not be a therapy that is suitable
7 for acute events.
8 So if you have an acute stroke, or if you
9 have an acute heart infarct, and you try to correct
10 that, there is no way that you can clone ESLs to
11 correct that, or you could create MAPCs to correct
12 that within the next one or two weeks.
13 It just takes too much time to try to do
14 this. Then you could argue, well, I will store our
15 own MAPC cell lines or own ESL lines just in case we
16 need it, which definitely I don't think is financially
18 So even though the ideal situation would
19 be to be able to make everybody's own cells, and I
20 think in the long term if the cell therapies are
21 proven to be, for instance, very useful in patients
22 who have a severe MI that you can actually correct
23 them almost immediately after the MI has occurred, or
24 within the next few weeks after it has occurred, it
25 almost has to be done on an allogeneic basis.
1 And in that case, trying to come up with
2 wise ways of making the cells acceptable to the vast
3 majority of patients, whether it is multiple cell
4 lines and a minimum amount of immunosuppression, or
5 establishing partial chimerism by creating both blood
6 cells and heart muscle cells from the same cell lines,
7 for instance, would be one way to get around that.
9 DR. KASS: Thank you very much. Thank you very
10 much for a wonderful presentation, and a very generous
11 and full response to our questions. If we might take
12 the liberty of just contacting you with some other
14 I know that your e-mail is full, and we will try to
15 add very little, but as we go along, we might have
16 some additional things.
17 DR. VERFAILLIE: That would be great.
20 DR. KASS: Thank you very much. Members are asked to
21 go immediately from here to the other room, where they
22 want a group photo, and the four or five of us who
23 have not yet posed for our individual mug shots, are
24 asked to stay. I think lunch will be served there.
1 We will reconvene here shortly after 1:30,
2 and let's say about 1:35 or 1:40.
3 (Whereupon, at 12:28 p.m., a luncheon
4 recess was taken.)
1 A-F-T-E-R-N-O-O-N S-E-S-S-I-O-N
2 (1:41 p.m.)
3 DR. KASS: Well, if I sing a song, or make
4 some announcements, maybe we will get the full
5 numbers, but this is the third of our three sessions
6 on stem cell research, having spent the morning
7 hearing two presentations on the science.
8 And we now turn in this session to ethical
9 questions in stem cell research, and we are very
10 fortunate to have as our guest Professor Gene Outka,
11 who is the Dwight Professor of Philosophy and
12 Christian Ethics at Yale University.
13 And for a long time one of our most
14 careful students of the ethics of biology and medicine
15 among many other things.
16 Apart from our interest in the merits of
17 the case, a paper written on a subject of concern to
18 us, I have confessed in the chairman's cover letter,
19 in a sentence which has a missing word, that I have an
20 additional purpose in mind here, namely as just as
21 those of us who are not experienced in science, need
22 practice in grasping the concepts and methods of
23 scientific analysis, so those of us who are not
24 experienced in ethics would need some practice in
25 working with the concepts and ways of ethical
1 analysis. And Professor Outka's work is nothing if
2 not careful, analytical and disciplined, and we are
3 very thankful that he could be with us to discuss his
5 All of us have had a chance to read it,
6 and I exhorted you to read it more than once, and
7 there is a lot packed in it. And Professor Outka is
8 going to lead off with a few remarks, after which I
9 have asked Michael Sandel to make comment that would
10 open our discussion. Thanks very much, Gene.
11 DR. OUTKA: Well, it is a great honor for
12 me to be here, and I enjoyed sitting in enormously in
13 the morning sessions, and noted that although the
14 focus was on scientific matters, moral matters also
15 arose from time to time, as when Dr. Gearhart told us
16 that he doesn't give the same moral status to the
17 embryonic entity as he does to the fetus.
18 And I think that illustrates one of the
19 claims that I actually make in the paper, which is
20 that on this subject, whether we like it or not, we
21 all have to be moralists in one way or another; that
22 certain moral determinations are unavoidable.
23 And in-part that is because the moral
24 positions that we take have such direct and sometimes
1 colliding implications for the policy and political
2 recommendations that we make.
3 And I contrast that with certain other
4 cases where you could have some theoretical debates
5 and disagreements might abound on that level, but you
6 could when you turned to practical and political
7 matters, you could come to some modus vivendi or
8 something of the sort, where the theoretical
9 disagreements don't translate into necessarily
10 practical political disputes.
11 That is not the case with this subject I
12 contend, and so we all have to be inclined to engage
13 in moral reflection, and although moral reflection has
14 its own esoteric features in the hands of at least
15 some, I think that this session may be more
16 egalitarian in a way, because I, like Samuel Johnson's
17 dictum, that we are perpetually moralists, but we are
18 geometricians only by chance.
19 And by that I take him to mean that moral
20 matters, that there is a fundamental equality about
21 our reflection on moral matters, and it does not
22 require a special talent in the same way.
23 So that then leads me to say a few things
24 about this paper, which we are going to discuss. I
25 tried to do several different things in it, and I
1 tried to give some kind of an account of some of the
2 major points of disagreement, and I have a spectrum of
3 views from the right to the center, to the left.
4 And I myself then plum for a particular
5 region of the center, and along the way though I do
6 try to show how debates about abortion and debates
7 about stem cell research converge and diverge.
8 And finally I propose a nothing is lost
9 principle, and let me say a little more about that,
10 but I think probably the most economical way to
11 proceed is simply to indicate for you some of the
12 normative conclusions that I put forward in the paper.
13 And not tarry over the questions about
14 whether I do justice to those either more conservative
15 than I am, or more liberal than I am. Spokespersons
16 for both positions can speak for themselves later on.
17 So let me just then lay out some of the
18 claims that I make, and that will get us started at
19 least. I make some claims about the status of human
20 life from conception forward, and I argue that once
21 conceived each entity is a form of primordial human
22 life that should exert a claim upon us to be regarded
23 as an end and not a mere means only.
24 And I say that it is one thing to allow
25 that we need not yet ascribe full moral standing or
1 equal protectibility to embryos. That is to say, I
2 deny that abortion and embryonic stem cell research
3 are morally indistinguishable from murder.
4 But I claim on the other hand that it is
5 another thing to instrumentalize embryos through and
6 through when what we intend in the actions we perform
7 exhaustively concerns benefits to third-parties.
8 And I take that to be one indication of
9 sheer instrumentalization, where the actions that we
10 perform we can only justify, and justify exhaustively
11 by virtue of benefits to third-parties.
12 That is to say that I deny that abortion
13 and embryonic stem cell research are morally
14 indifferent actions in themselves to be evaluated
15 wholly by the benefits that they bring to others.
16 I then go on to conclude that to conduct
17 research on embryos that creates them in order to
18 destroy them clashes directly with the judgment that
19 entities conceived have irreducible value.
20 So that is on the one hand. I want to say
21 that the case for sheer instrumentalization is to be
22 resisted, but on the other hand, I also think that we
23 don't confront a single either/or as some
24 conservatives and some liberals suppose, to the effect
1 that we should forbid all embryonic stem cell
2 research, or we should permit it all.
3 I consider instead a more nuanced
4 possibility, or at least I think it is more nuanced,
5 where we may distinguish creating for research and
6 only employing for research.
7 And the latter of employing for research
8 allows us to consider in vitro fertilization as a
9 practice in our culture, and employing for research
10 connects with the datum of discarded embryos, where I
11 want to say that the original creation of embryos has
12 a non-instrumentalist rationale, namely the promotion
13 of fertility.
14 So that what we intend does not
15 exhaustively concern benefits to third parties. But
16 yet the aftermath allows us to pursue benefits to
17 third parties when we may do so without from the start
18 creating in order to disaggregate.
19 And the way that I try to speculate about
20 the pros and cons of this conclusion is to invoke the
21 nothing is lost principle, which I think illuminates a
22 morally significant distinction between creation for
23 research and employment for research.
24 The nothing is lost principle says that we
25 may -- that although it takes the prohibition against
1 murder seriously, it allows two exempting conditions.
2 The first is that the innocent -- that some innocent
3 will die in any case, and the second exempting
4 condition is that other innocent life will be saved.
5 And applying that to the matter at hand, I
6 say that we cannot choose whom we save in the case of
7 discarded embryos. They will die if we do nothing.
8 And we cannot save them by killing others
9 or letting others die. Yet, we may save others by
10 virtue of the research. And yet on the other hand,
11 and why this remains incurably in the middle, while
12 the nothing is lost principle permits attention to the
13 possible benefits to third parties from research on
14 discarded embryos, it does not permit the concern
15 about the status of embryos to recede to a platitude.
16 And where such concern never has efficacy
17 and can always be trumped, and that is one of my tests
18 about saying that a commitment to in this case
19 embryonic life is serious only if it trumps something
20 whenever there is a conflict.
21 It does not have to trump on all
22 occasions, but it has to trump on some occasions. And
23 where I want to say it trumps is where it disallows
24 the creation of embryos only and exclusively for the
25 sake of, and in order to, disaggregate them.
1 I speculate on some of the difficulties
2 that this position generates and trying to face those
3 I hope honestly. Some of the difficulties I regard as
4 more demanding than others, but I do rehearse some of
6 But I think it would take us too far a
7 field to review those now. So let me just content
8 myself with having summarized that part of the case.
9 DR. KASS: Thank you very much. Michael
10 Sandel will lead us off with some prepared comments.
11 Thank you.
12 PROFESSOR SANDEL: Well, let me first of
13 all add my thanks for really a fine paper that has so
14 many virtues of the best work in moral philosophy, and
15 its close reasoning, and its careful reasoning, and in
16 it directing our attention to some really central
17 moral questions.
18 And it also has, the paper does, and the
19 proposal of the appeal of staking out a middle ground,
20 of trying to find an alternative to either/or
21 positions, that it exudes the spirit of compromise,
22 which is appealing in and of itself.
23 And more than that, the kind of compromise
24 that it offers has a certain kind of intuitive appeal,
25 which is faced with these hard moral questions about
1 the status of embryos, it is on the other hand the
2 goods to be had from research and possibly curing
4 And the intuitive appeal is to say, well,
5 the spares, the excess embryos left over from IVF
6 clinics, they are going to die anyhow, and so we may
7 as well get some good use out of them and do some
9 But we shouldn't therefore consider it
10 morally permissible to create for the sake of the
11 research or curing of diseases new embryos. We should
12 just use the spare ones and that is the nothing is
13 lost principle.
14 There is something very appealing about
15 that compromise and intuitively persuasive. But since
16 I don't find it persuasive, I want to see if I can
17 press a little bit and offer a concrete case to
18 illustrate why I don't think the principle works, or
19 is persuasive.
20 The first thing to notice -- and this
21 struck me I think only maybe in my second reading of
22 the paper -- is that the distinction, the crucial
23 distinction is not as we might think from our common
24 discourse about these subjects, between fertilized
25 eggs left over from the -- well, the distinction isn't
1 between the IVF fertilized eggs, or embryos, on the
2 one hand, and cloned ones on the other.
3 To the contrary, the morally relevant
4 distinction here cuts across the distinction that we
5 are familiar with between the ones that come from the
6 IVF clinics, and the ones that are created as clones.
7 Because the crucial distinction is why the
8 embryo was created. So if we imagine an embryo, a
9 cloned embryo, created for reproductive purposes, and
10 then we consider it spares in that process, it would
11 be all right to do research on those cloned ones,
12 provided that they were created for the sake of
14 But it wouldn't be all right to use cloned
15 embryos created for the sake of research. Likewise,
16 it would be all right to use embryos created with
17 sperm fertilizing an egg in an IVF clinic, provided
18 that it was created for the sake of reproduction.
19 But it wouldn't be all right to use an
20 embryo created when a sperm is brought together with
21 an egg in sexual reproduction in a clinic if the
22 purpose of the clinic bringing the egg and sperm
23 together was to create an embryo for research.
24 So the key here, and what is carrying the
25 moral weight, is not how the embryo was created, but
1 why. Scientists may use excess embryos, however
2 created, provided that they were created for the sake
3 of reproduction. But scientists may not use embryos
4 created for the purpose of research or curing
6 Then the question arises why or the
7 reason, or the motive for creating the embryo
8 determines whether it is permissible to use them for
9 research into diseases.
10 Now that is the heart of the question; why
11 the motive matters, and why the motive for the
12 creation makes a moral difference. And the way to
13 explore this question would be to put aside cloning
15 Let's imagine two cases; of traditional
16 sexual creation of an embryo, or in a clinic, or in a
17 lab. In case one, a woman comes to an infertility
18 center and donates some eggs because she wants to help
19 infertile couples have a genetically related child.
20 And the clinic brings together her eggs
21 with donor sperm and creates some embryos, some of
22 which are implanted, and some of which wind up being
24 In case two, a woman goes to a clinic or
25 to a lab, and donates eggs for a different reason.
1 She donates them because she wants to support stem
2 cell research to cure Alzheimer's and Parkinson's.
3 Her eggs are brought together with donor
4 sperm, and made available to scientists who are
5 engaged in this research.
6 In both cases, the motive of the woman who
7 contributes or who donates the eggs is to advance a
8 worthy end; helping an infertile couple have a
9 genetically related child in the first case, and
10 advancing scientific research in the other.
11 And in both cases, she contributes knowing
12 that at least some of the embryos created from her
13 eggs will be sacrificed, will be discarded or
15 Now, according to the nothing is lost
16 principle, what do we say about the availability of
17 these two embryos, or sets, or batches of embryos for
19 Well, the nothing is lost principle in the
20 paper tells us that it is okay for scientists to
21 extract stem cells from the first batch, but not from
22 the second. And the question that I have is why.
23 The answer that the paper seems to give
24 is, well, in the first case, they are spares. They
1 are excess embryos. But then it is not so clear to
2 me what counts as spare.
3 Well, strictly speaking, a spare is an
4 embryo not needed for reproduction that is going to
5 die anyhow. So we may as well use it for some good.
6 But by that definition of a spare, both batches of
7 embryos are spares.
8 Once they exist, they both meet the
9 nothing is lost principle. It is true that both
10 batches of embryos that we have here are going to die
11 otherwise, and we might as well get some good use out
12 of it.
13 So that can't be -- well, maybe that is
14 too limited of an account of what you mean here by
15 spare embryos, because by that definition they would
16 both be spares, both batches.
17 So maybe there is a further condition of
18 an embryo being a spare embryo; namely, that it had
19 been created in the first place for the sake of
20 reproduction. That would limit us to batch one.
21 But then the question is whether that
22 condition adds any moral relevance or interest. The
23 idea must be that the intention of the donor confers
24 some morally relevant difference.
1 Moreover, a morally relevant difference
2 that somehow filters all the way down to govern what a
3 scientist may morally do. Well, what could that
4 difference be?
5 How could the motive, the different
6 motives in these that led to the creation of these two
7 batches of fertilized eggs, or of embryos, how might
8 that work? Why would the motive make a moral
10 Well, there are at least two possibilities
11 that I see from the paper. Maybe the motive makes a
12 difference in the moral status of the embryos that
13 result. Maybe it makes a difference therefore in the
14 respect that the embryos are due. But why would that
16 How does the different motive in the two
17 cases confer different moral status on the embryos in
18 batch one than in batch two, such that the ones in
19 batch one are properly open to use, to be sacrificed
20 for a worthy scientific end, but not the ones in batch
22 There doesn’t seem anything different in the
23 moral status of the embryos in batch one and batch
24 two. Well, maybe the difference then isn’t in the
1 moral status of the embryos that result from these
2 different motives.
3 Maybe the difference is in the way that the
4 scientist who would do the research is complicit in
5 the destruction of the embryos that is a necessary
6 feature of the research. But how does the motive that
7 the donor had in creating the two batches change the
8 degree of complicity of the scientist?
9 And here I am drawn to our Footnote 12, which
10 cites our colleague, Gil, in a question that he put,
11 which I think is a perfectly relevant question here if
12 you are trying to work out some difference in the
14 Just because there are some embryos that
15 somebody else has decided to destroy or to discard,
16 why does that remove the complicity of the scientist
17 who does the killing, and Gil’s example, who is cited
18 in the paper, seems to me to be a very good one.
19 If the Nazis decided to gather people in the
20 concentration camps and had determined that they be
21 killed, it wouldn't -- that fact that they were going
22 to die anyhow, wouldn't justify a doctor coming and
23 yanking out their organs to save some innocent people.
24 He would not be less complicit or she,
25 that doctor, in doing or in yanking out their organs
1 to do a good thing simply because somebody else had
2 decided that those people would already be killed,
3 regardless of how you regard the moral status of the
5 It seems to me the degree of complicity
6 isn't affected by the motive of the person who created
7 the embryo in the first place. Well, the only other
8 possible answer that I can think to the question why
9 does the motive of the donor confer some morally
10 relevant difference on these two batches, is -- well,
11 maybe to recur to the underlying intuition of the
12 paper, which is that embryos should be treated as
13 ends, and not only as means.
14 And therefore to sacrifice excess or spare
15 embryos in connection with IVF is morally permissible,
16 because the donor didn't know which of the embryos
17 created would be sacrificed, i.e., treated as a means,
18 even though the donor knew that some would be.
19 But even if that marks out a morally
20 relevant difference for the donor, and the donor's
21 willingness to sacrifice embryos for the sake of
22 various ends, it is not clear how this makes the
23 embryo that results more open to use by the scientist.
24 So my question is going back to these two
25 scenarios, these two batches, created for different
1 motives, to test my motive matters, is what moral
2 difference does the motive make.
3 DR. KASS: We have to decide on a
4 procedure it seems after a wonderfully rich comment
5 like that. The only fair thing to do is to ask Gene
6 if he would like to respond now or later.
7 DR. OUTKA: Well, I think it was a
8 wonderfully rich comment, and probably since it was a
9 rather complicated one, it might be best at least to
10 maximize the chances that I will forget less of it if
11 I go ahead and respond now rather than wait, because
12 there are a number of points that come up.
13 And I thank you very much for your care in
14 putting these questions to me. I guess I don't really
15 want to use as you suggest -- and I don't use I think
16 the language of motive. There is a wide question
17 about why the embryo is created, but I don't think
18 that is satisfactorily accommodated by calling it a
20 What I wanted to do was two things. I
21 wanted to take seriously the notion of the injunction
22 that comes to us in religious traditions, but also in
23 some philosophical ones, above all, Kantian ones, that
24 treating people as ends and not merely as means.
1 And I wanted to say that that generates a
2 certain case for inviolability, and so I connected
3 that injunction to the ethics of killing. So the
4 first thing that we are talking about I think is more
5 the morality of actions, rather than the morality
6 simply of motives.
7 And I want to say that certain actions may
8 be licit if one can say that the rationale for
9 -- let's say in the case of IVF clinics, being in the
10 mess that we are in with respect to them doesn't have
11 to do with actions that we ourselves perform.
12 We are actually dealing with the after
13 effects of an entire industry, and so that would
14 already distinguish the status of what we are
15 contemplating there from the status of contemplating
16 a direct action ourselves when we do X in order to do
18 And I want to say that a prime case for
19 treating an entity as instrumental through and through
20 is when we do X in order to destroy them for the sake
21 of the benefits that destruction will bring to third
23 I want to say that that is an
24 instrumentalist action through and through. So I
25 would prefer to use the language of ends and means,
1 and the morality of actions, and specifically the
2 prohibition against killing, rather than I think the
3 language of motives.
4 And which does not seem to me to quite
5 capture those points. Now, in regard to your very
6 interesting example, of case one and case two, it
7 would be the case that if a woman donates eggs for
8 reproduction, she there is donating her eggs for an
9 end that isn't menial.
10 I mean, there she is donating her eggs for
11 the sake of a couple who want a child, and so nothing
12 that the couple contemplates, or nothing that she does
13 contributes to a case for creating in order to
15 Whereas, if she gives her eggs to support
16 stem cell research -- and that is her only reason, so
17 that she is giving her eggs in order to do that --
18 there it seems to me that she runs the risk of
19 violating the thing that I am objecting to, which is
20 creation in order to destroy.
21 So the relevant fact is not simply that
22 they are both spares. The relevant fact has to do
23 with the morality of the two different kinds of
1 And where the ends have to then be also
2 distinguished, and you say that both ends are worthy.
3 One is to help a couple, and one is to promote
4 research. But I am precisely objecting to the second
5 kind of so-called worthy end if it means that you may
6 directly create a life in order to destroy it.
7 That seems to me to be a trumping action;
8 that is to say, the objections against a trump, the
9 good aim of promoting research. Whereas, nothing
10 about helping a couple involves a creation in order to
11 destroy. So it is not subject to the same kind of
13 Now, you also then list some possibilities
14 about how these different cases might be distinct. I
15 think the batch one and batch two -- I hope that I
16 have given a different account of why I make a
17 distinction between those two cases.
18 Your reference to Gil Meilaender is a very
19 important objection to me in correspondence about
20 whether or not nothing is lost allows to much or
21 permits too much.
22 I strain there, and I grant that I strain,
23 but what I want to argue is that in the case of
24 embryos slated for destruction, and who are frozen in
1 perpetuity, or eventually to be discarded, we have a
2 peculiar condition of perpetual potentiality.
3 And that distinguishes them from some of
4 the other possible uses of nothing is lost, which I
5 disallow. So there the argument would be that they
6 are the peculiar features of entities that are
7 characterized as having perpetual potentiality that
8 distinguishes them.
9 That is not certainly an adequate reply,
10 but that would be the shape I think of my general
12 DR. KASS: Michael, please come back and
13 maybe one more round would help, and other people
14 would like to get in on this.
15 PROFESSOR SANDEL: Well, there are two
16 issues here. The last point was an attempt to show
17 that in the first case the woman who donated an egg to
18 help a childless couple, that her act was morally
20 Whereas, the second woman's act was not
21 morally permissible because it instrumentalized the
22 embryo in a way that the first one didn't. Now, that
23 is one issue, and I would like to come back to that
24 issue maybe later.
1 But even if you are right about that, it
2 still would be true that the nothing is lost
3 principle, from the standpoint of the scientist, must
4 regard both batches of embryos as spares in the
5 relevant sense that they are going to be discarded or
6 destroyed anyhow, and why not derive some good from
8 So even if you made out the first
9 distinction between the acts of the woman donor, and
10 there are questions about that, but independent of
11 that, still how does that limit or change the scope of
12 the scientist's responsibility, such that -- there are
13 certain eggs or the eggs in batch one, because they
14 were not conceived instrumentally, are open to use.
15 Whereas, the eggs in batch two, the
16 embryos in batch two, because they were conceived
17 instrumentally, are not open to use. Why is that?
18 DR. OUTKA: Well, the key thing there I
19 think I think is that I was talking about the
20 rationale of in vitro fertilization clinics by and
21 large, and rightly or wrongly, characterize that
22 rationale as being able to sort of claim that.
23 Their dominant aim was to address the
24 problem of infertility, and not to provide embryos for
25 research. That is the overall generalization, and I
1 know that there are a lot of questions to be raised
2 about that, and at the very end of the paper, in the
3 last version of the paper, I raise some of those
4 questions myself.
5 But nonetheless I would stick to that. So
6 I would think that your second case, your second
7 batch, would not come up very much. I mean, I am
8 obliged to you for thinking that it might. I guess I
9 was talking about in vitro fertilization with that
10 overall rationale.
11 You are talking about women who would
12 donate their eggs simply to support stem cell
13 research, and they would do that independently of
14 whatever the scientist did.
15 And I would agree that in such a -- and I
16 think they are pretty rare cases though, that
17 scientists would not be complicit.
18 PROFESSOR SANDEL: They are rare only
19 because IVF happened to get going sooner, and it has
20 generated a hundred-thousand of them. But once stem
21 cells get going, there is no reason to think that
22 there won't be a hundred-thousand of those out there.
23 DR. OUTKA: I doubt it very much. I mean,
24 there are lots of questions actually about the
25 pressure placed on women to donate eggs, and the
1 morality of egg donation is actually I think a really
2 important subject that has not been discussed by
4 But the important point here is that since
5 you don't have such a class, what I am objecting to
6 are researchers, scientists, who become complicit
7 because they themselves do the creating.
8 PROFESSOR SANDEL: Through cloning, but
9 morally speaking, what do you say about the case where
10 a lab takes or invites women to donate eggs, whether
11 it pays them or asks them to donate them for the
12 purpose of stem cell research?
13 DR. OUTKA: If it is inviting them, I
14 would have to look at that. To the extent that it
15 takes initiative, to that same extent it becomes more
16 complicit, and therefore more subject to the objection
17 that I am raising.
18 PROFESSOR SANDEL: But you would agree
19 that from the scientist's point of view how it got
20 there, whether it was from someone who gave it for
21 reproductive purposes, or from someone who gave it for
22 stem cell research purposes, from the scientist's
23 point of view, do you think that makes a moral
1 DR. OUTKA: Well, I do if they are
2 inviting a woman to donate eggs so that they may take
3 those eggs and fertilize them in order to destroy them
4 for the sake of, and so yes, then they are complicit.
5 PROFESSOR SANDEL: Well, the lab. I am
6 assuming the lab does and then the scientist goes and
7 gets the -- whether the scientist, or whether she goes
8 to the lab and says give me some of your spares from
9 reproductive donations, or says give me some of your
10 spares from people who actually wanted their eggs to
11 go to this purpose, do you think it is worse in the
12 second case for the scientist to do that?
13 DR. OUTKA: I think it is worse whenever
14 there is an active role played in an action which I
15 regard as disallowed for reasons given. Now, there
16 are a lot of nuances here, and I know that there are a
17 lot of conservatives who think as I say in the paper,
18 there will be some colluding going on between people
19 who run in vitro fertilization clinics, and scientists
20 who want spare embryos.
21 And I agree that there is a kind of
22 performative problem there, and I tried to discuss
23 that. So I am not saying that there aren't shades
24 here, but the spirit of the paper is this.
1 That we do have an action where we are
2 creating in order to destroy something, and that does
3 seem to me that it should give us pause. It is not
4 the same, and it won't simply be justified by saying,
5 well, look at all of the third parties who are going
6 to benefit.
7 If that is what we are saying about it,
8 and we are creating in order to destroy for that
9 reason, then let's say it very clearly. But let's say
10 that we are then treating some entities totally
11 instrumentally, and make no bones about it.
12 That is the first part of the spirit of
13 the paper. The second part is to say, all right, it
14 is the case that there are enormous benefits to be
15 derived from embryonic stem cell research.
16 Let's see whether or not we can mount a
17 consistent moral argument that will allow us to draw
18 on some of those, but to keep some limits, so that we
19 are not simply tolerating anything, or losing all of
20 our criteria for distinguishing.
21 That is the spirit of the paper. Now,
22 some of these cases will involve as I say gray areas,
23 but I don't think that those gray areas by themselves
24 will invalidate that two-fold part of the case as
1 PROFESSOR SANDEL: Just a brief reply. If
2 doing something to help a third-party is
3 instrumentalizing, then all of the embryos in batch
4 one are also morally impermissible because we are
5 imagining a case where the woman goes to the
6 infertility clinic to donate her egg for the sake of a
7 third-party, for the sake of another couple having a
9 So that is doing a good thing for a third-
10 party, and so that is instrumentalizing isn't it in
11 just the same way as the second case?
12 DR. OUTKA: But there is no killing
13 involved. She is donating her eggs in order that they
14 may take those eggs and fertilize. That is life
15 enhancing. This is as I said --
16 PROFESSOR SANDEL: Provided that there are
17 no spares that are destroyed.
18 DR. OUTKA: No.
19 PROFESSOR SANDEL: The issue arises only
20 because -- if it were a one for one, if there were no
21 spares, no excess, then the issue wouldn't arise. We
22 are talking about the woman making the donation to
23 help the third-party have a genetically related child,
24 knowing that there will be some fertilized egg, some
1 embryos, that will be sacrificed, discarded, as a
2 consequence of her doing that.
3 DR. OUTKA: But you know how long, and
4 perhaps too long in the paper, that I agonized about
5 precisely that recognition. That that is a case where
6 we foresee under present circumstances that more
7 embryos will have to be created for promoting this end
8 of conception, and fertilization, than we would like.
9 But we say that we foresee that, but we
10 don't directly intend it, and there is still a claim
11 that I think needs to be -- I would still want to try
12 to make, which is that there is a morally relevant
13 difference between foreseeing the inevitability of
14 excess embryos, and lamenting that, and wanting it
15 over as soon as we can, et cetera.
16 And creating again in order to kill, or to
17 destroy, and I still think that there will be a
18 difference there.
19 DR. KASS: There is a long queue that is
20 prompted either by the paper or the comments. I have
21 Jim Wilson, Mary Ann Glendon, Alfonso Gomez-Lobo.
22 PROFESSOR WILSON: Let me begin with the
23 language of motive, because though he may not have
24 intended it, I think Professor Outka has in fact used
25 the language of motive on page 24, where he talks
1 about creating an embryo exclusively for research, the
2 motive of the person.
3 Or creating it exclusively for fertility,
4 the motive of the actor; and then again on page 35,
5 creating for research, motive, and creating for baby
6 creation, motive.
7 I think it is well to get the word motive
8 out of our language. I hope that Mary Ann Glendon
9 will forgive me if I use an inept legal analogy, but
10 in the criminal law, we don't ordinarily determine
11 guilt or innocence on the basis of the motive.
12 The man lies in wait to kill a woman, and
13 shoots her from a distance, and approaches closely to
14 make sure that she is dead, and finishes her off with
15 several bullets to the head.
16 We don't ask in the court whether he did
17 it to collect her insurance or to prevent her from
18 carrying on her experiments in dogs, since she happens
19 to be a biologist at a local university laboratory.
20 We might take motive into account in the
21 sentencing decision, but that would be up to the
22 probation officer. It seems to me that to modify the
23 circumstance that Michael laid out for you and with
24 which we have been struggling, suppose now the woman
1 donates eggs in an IVF clinic, and they are all
3 And suppose before picking the egg she
4 wishes, she does what I think is in fact not
5 impossible, and may indeed be commonplace, she has
6 each fertilized egg tested for its likely hair color,
7 or intelligence, or sex, or whatever of the embryo
8 that will be produced.
9 And having selected the egg she wants and
10 has it in place, she looks at the other people and
11 says kill the rest. In fact, particularly kill those
12 two. One is going to have Down's Syndrome, and the
13 other one is going to have cerebral palsy.
14 Doesn't that put the IVF eggs in exactly
15 the same position as the eggs created by a woman who
16 has done it solely for the purpose of creating somatic
17 cell nuclear transfer for the purposes of biomedical
19 In fact, does it make it worse, because
20 now not only are the eggs that she has picked out with
21 the doctor's consent going to be destroyed, they will
22 not be destroyed in a way that will help anyone else.
23 So that to me the leftover egg solution to
24 this problem doesn't work. The leftover egg solution
25 doesn't solve the moral difficulty.
1 DR. OUTKA: Shall I try to respond to each
2 of these as I --
3 DR. KASS: Well, I think that these are
4 all solid, and --
5 DR. OUTKA: Oh, yeah, very solid. I am
6 indebted to you all, and let me say though that I
7 think the statements that you read really are
8 precisely about motive.
9 Let's maybe use the language that is
10 closer to what I actually use in the paper, which is
11 intention rather than motive. Now, I have always been
12 drawn to an old assumption about the doctrine of
13 double effect.
14 I am not sure that it is going to work,
15 but I have always been fascinated with this claim, and
16 I think there are some cases where it worked, but it
17 doesn't always work.
18 And that is that certain action
19 descriptions entail certain intention descriptions.
20 Now, that is much closer to the timbre of my argument
21 than the language of motive, because what I want to
22 say is that an action, where you actually create in
23 order to destroy, if you describe that action, it is
24 hard to avoid identifying one intention.
1 And that intention is to destroy, and so I
2 don't -- I am going to continue to try to resist of
3 saddling me with the language of motives here, and I
4 don't think the statements that were cited really do
6 Let's think about intentions with respect
7 to actions more than about general motives. With
8 respect to your case, Professor Wilson, of all of the
9 eggs fertilized. That it seems to me is -- I have
10 gotten a little bit of a bee in my bonnet about this.
11 The suppose this or suppose that, as a
12 kind of test for measuring the adequacy of an
13 argument, this hypothetical case that you cite is I
14 think not at the moment within the realm of
16 So I am not sure that I have -- that I am
17 obliged to respond to it in precisely the terms that
18 you have set it out. The fact of the matter is that
19 we do have a situation where one of these embryos is
20 going to be chosen to be implanted and brought to
21 term, and the others will not be.
22 That is the datum that we are dealing with
23 in trying to make moral sense of, and I would have to
24 stick with that one, rather than speculate on all of
25 the eggs being fertilized, and then if she chooses
1 only one, rather than all of them, she is guilty for
2 what she does to the other.
3 I think that changes the terms of the
4 example so far that it is not any longer precisely
5 comparable as a test of what at least I want to argue.
6 DR. MCHUGH: Leon, I have to interrupt
7 just for a second. I just don't understand when you
8 say the intention, or any intention, is in order to
9 destroy. Nothing is being made here in order to
11 Will you explain that a bit further? I
12 just got stuck on that. In none of these cases is
13 anybody creating anything in order to destroy.
14 DR. OUTKA: That is a very important point
15 and thank you for mentioning it.
16 DR. MCHUGH: Sorry to interrupt.
17 DR. OUTKA: No, no, no, I'm glad you did.
18 If I am wrong about this one, then a lot of things go
19 by the board, and I could be wrong about this one. I
20 actually had wrung my hands about it quite often.
21 It involves a description of what is done
22 that does include my importing a kind of conclusion
23 about what is in effect going on that researchers
24 might not immediately consent to.
1 But it does seem to me that if you ask a
2 researcher why are you creating this entity, and the
3 answer is, well, I want to do something to it, which
4 will certainly kill it, but I am doing it for the sake
5 of third-parties.
6 Then that seems to me to be an instance of
7 instrumentalizing it. So the in order to destroy, or
8 in order to disaggregate, is internal to the
9 description of the act I want to argue. Now, one
10 might try to get at the position by challenging that,
11 but it is hard for me --
12 DR. MCHUGH: You just used the word
13 intention, that it was intention in order to destroy.
14 I mean, you had several intentions.
15 Perhaps, and I might accept that, but there were
16 several intentions involved here. But you put it all
17 on the basis of in order to.
18 DR. KASS: Could I lend a hand on this? I
19 mean, had you not raised the question, I would have at
20 some point.
21 DR. MCHUGH: I am sure that you would
23 DR. KASS: But I think I can -- if I am
24 right, Gene, let me have a try. I think the proper
25 way to state the intention is we create these embryos
1 -- and by the way, I don't think this paper is
2 primarily -- I don't think it is at all about somatic
3 cell nuclear transfer.
4 I think the question really should be
5 taken up universally, regardless of how the embryos
6 come to be. I think that Michael is right about that,
7 and this paper was written without even a reference to
9 But the researchers -- and there have been
10 people who have come forward to -- well, people have
11 come forward to donate their eggs and embryos for the
12 sake of research. And the researchers who go to work
13 on that wouldn't say that we want these embryos in
14 order to destroy them.
15 We want these embryos because we want to
16 use their stem cells for understanding or for
17 treatment. But it is the unavoidable and inescapable
18 entailment of that intention that the embryo be
19 destroyed in the process.
20 If there was some way in fact to get the
21 stem cells without destroying the embryo, people would
22 be delighted I assume. And it seems to me that you
23 can make the same case as follows.
24 This is not to say that the embryo is the
25 human being, but if you were to say that you too, out
1 my heart in order to save my friend, Wilson, here who
2 needed a transplant.
3 And that you weren't taking out my heart
4 in order to destroy me. All you were really trying to
5 do was to save him, but if there was no way to do that
6 without destroying me, then that material fact of your
7 intent becomes embraced in the overall act with great
9 So I think that I myself would not
10 describe this as saying to create it in order to
11 destroy it. I would create it in order to do
12 something else, but the necessary and inescapable
13 entailment of which is the destruction, and therefore
14 you embrace that intrinsic aspect of the act.
15 I think that is a better way to do it and
16 it doesn't try to gain mileage, if you don't mind,
17 from a more lurid expression that implies that the
18 people are in the destruction business because they
19 like destruction. I don't think that is the flavor or
20 the intent.
21 DR. OUTKA: No, I take that as -- I will
22 regard that as a friendly amendment, and certainly
23 agree with it. I think the reason that I used that
24 language was simply to underscore that it is
1 unavoidable that we can't ignore this as part of a
2 full characterization of the act.
3 DR. KASS: Sorry to have intruded. I want
5 DR. OUTKA: That was very helpful. Thank
7 DR. KASS: I have Mary Ann.
8 PROFESSOR GLENDON: Well, doctor, you were
9 very kind when you started out to adopt an egalitarian
10 approach, and suggest that we are all on a equal
11 footing with respect to the moral dimensions of these
12 very difficult problems.
13 I must say that I feel a little backward
14 maybe because I am a lawyer, but I am still -- from
15 the very beginning, from my very first meeting, I have
16 been struggling with a problem that maybe you can help
17 me with.
18 I am having a hard time seeing the
19 difference between what is done -- forget about motive
20 and intention, but what is done in in vitro
21 fertilization, and what is done in creating an embryo
22 for research purposes, and let me explain why.
23 I think that in both cases the procedure
24 is done with full knowledge that embryos will be
25 destroyed. Now, many people, and not just at this
1 meeting, but at previous meetings, many people have
2 said that the difference is that in vitro
3 fertilization is done for a worthy end.
4 And I think you or Professor Sandel said
5 to help couples with infertility. Well, we all know
6 that that is not quite right. That very often it is
7 not couples. I don't know whether couples are
8 predominantly the ones, but certainly a large
10 But leaving that aside, there are a number
11 of factors that I can think of that to my mind call
12 into question a casual assumption that what we are
13 dealing with here is such a worthy end that it would
14 justify the destruction of embryos.
15 I will name some of them. One is -- and I
16 am naming these as a constellation, and not that each
17 factor would be decisive in and of itself. But it is
18 an extraordinarily expensive procedure.
19 It is highly uncertain in outcome. It has
20 unknown long term health effects for women who are
21 subjected to massive doses of hormone injections, and
22 the evidence coming out now is suggesting that
23 children born from this procedure may have an unusual
24 proportion of defects and disabilities.
1 And then finally as I said, it involves
2 creating an embryo with the certain knowledge -- or
3 creating embryos with the certain knowledge that some
4 of them will be destroyed.
5 So I guess that my problem is that not
6 only that I wonder how that can be easily said to be a
7 worthy end, and then I guess more seriously, if we
8 accept the creation of embryos with the certain
9 knowledge that they will be destroyed for purposes of
10 in vitro fertilization, doesn't it become or haven't
11 we gone very far down the road indeed toward
12 justifying the creation of embryos for research
14 DR. OUTKA: Well, I thank you very much
15 for that question and I think it is forceful and
16 important. And my perhaps only flagellations at the
17 end of the paper suggest that I feel its force.
18 But for better or for worse, let me at
19 least sketch the lines of a reply, even though I don't
20 think this addresses all the things that need to be
21 addressed in your important set of objections. One is
22 that I do think that there are two things in conflict
23 here. One is infertility, and the other is excess
24 embryos, and we welcome neither. I think that is
25 where we have to begin.
1 But I indicate that the datum leaves me
2 deeply disquieted, and I don't easily assume that it
3 is simply a good. I agree with you that it is
4 expensive and uncertain.
5 It nonetheless is something, and I have
6 talked to a few people who have been through it, and
7 who have actually -- it has resulted for them in
8 children, or grandchildren, and they are nonetheless
9 very thankful for it.
10 But I suppose the spirit again of my
11 approach is to say, look, this is a practice about
12 which there are many, many questions. But I am a
13 little uneasy with the grand -- now that a lot of
14 people are beginning to realize this, and are quickly
15 denouncing it, they often use the language of we.
16 That we are responsible for this, and this
17 isn't like a contingent disaster. This is something
18 that we have created by our own hands, and I would
19 register a slight disquiet with that, too, because I
20 don't think that we did it.
21 I think that most folks who have the gift
22 of fertility don't worry very much about this. And so
23 this was developed -- and I agree that we didn't
24 object to it, or resist it, but it was developed by
25 people with vested interest in it, both the infertile
1 and those would were prepared to create these
2 industries in order to address that problem.
3 And now it is time it seems to me to air
4 whether or not the current arrangements can be
5 justified, where you have 10,000 new spare embryos
6 being created every month, et cetera. I mean, there
7 are a lot of questions that have to be asked.
8 But I would also say that in the case of
9 nothing is lost, I do observe that nothing is lost
10 sometimes can be justified even in response to an evil
12 I mean, there are some interesting cases.
13 For instance, in Jewish rabbinic literature, about
14 acquiescing to the demands of the tyrant under certain
15 circumstances. So you can invoke that nothing is lost
16 even when you don't think that the situation that got
17 you to here is admirable, or free from a certain
18 amount of evil.
19 And I think that it is in that spirit that
20 I will want to say that however we got here, and
21 whatever we should do from now on, we do have this
22 datum of a hundred-thousand embryos frozen in
23 perpetuity, or slated for destruction, and we do have
24 to reflect about that.
1 I am not sure that is a very satisfactory
2 reply, but it is to evidence a good deal of sympathy
3 with your reservations, without I think ignoring that
4 one datum.
5 DR. KASS: Gil Meilaender.
6 PROFESSOR MEILAENDER: Gene, as you know,
7 I think it is a very nice paper, and as you also know,
8 that doesn't mean that I have no questions about it.
9 And there are several things that I wanted
10 to ask about, but I want to stick with the nothing
11 more is lost, because it is central to your case, and
12 which I take it to mean -- I mean, if we were thinking
13 about what other kind of language would we use to
14 describe that, it means with respect to the particular
15 human subject, human entity, that we are talking
16 about, that there is nothing that we can do that would
17 further diminish its life prospects. I mean, that is
18 just by the nature of the case.
19 DR. OUTKA: And also nothing much we can
20 do to help its life prospects.
21 PROFESSOR MEILAENDER: Yes. And there are
22 a number of analogies that we might think of. I want
23 to come around to one of them in particular, but there
24 are a whole number; the condemned person, whose last
25 appeal has been lost; the irretrievably dying person,
1 who has only days to live; the permanently unconscious
2 person; the fetus in the process of abortion, or after
3 a decision for abortion has been irrevocably made.
4 I mean, there are a whole number of such,
5 but let's take the anencephalic infant. I take it
6 that there is nothing that you can do to further
7 diminish its life prospects.
8 I don't know whether you are prepared to
9 think that under those circumstances that it may be
10 instrumentalized for various research purposes, but I
11 would like to sort of hear you reflect on it, since in
12 a certain way it almost seems to me that the case
13 might be stronger for that than for the spare embryo.
14 The spare embryo is sitting around waiting
15 to be instrumentalized because we made some choices.
16 The anencephalic infant is just there. I mean, it is
17 not any choice of ours that got it there, and it
18 almost seems to me that the argument would be
20 So I would just like to hear you reflect
21 on that, and see how you would think about that in
22 relation to the kind of argument that you make.
23 DR. OUTKA: I know that is a first-rate
24 question, Gil, and since the anencephalic infant case
25 came up in connection with that suggested in your
1 correspondence to me, I should have been more careful
2 probably in how I used it.
3 My unsatisfactory response to this is that
4 I see the logic of saying that in some ways, since we
5 didn't have a role in bringing this about, there might
6 be greater warrant for using it.
7 But I guess the context of my discussion
8 of that, of pairing them, was the context only of
9 saying that we are unable to do anything for them.
10 That there is a kind of cessation of the injunction to
11 treat them as ends rather than means. We are limited
12 in what we can do.
13 Our love can't affect very much, and I
14 really only wanted to make the comparison in that
15 connection. I didn't want to sort of suggest that in
16 such cases that it would be quite all right to go
17 ahead then and use anencephalic infants for research
19 But I think that you are right in
20 suggesting that that would have to be a loophole that
21 I would have to close. I mean, I am worried about
22 this datum of the hundred-thousand spare embryos.
23 I mean, there is a kind of overwhelming
24 fact to go back to the earlier question that I think
25 we need to say something about. Is there anything
1 that we are doing that is preferable morally by
2 freezing them in perpetuity.
3 And my one place where I do not understand
4 the conservative concern about them is that I don't
5 know what people who don't want to destroy think they
6 are saving that is significantly different --
7 PROFESSOR MEILAENDER: Gene, can I just
8 make one suggestion?
9 DR. OUTKA: Yes.
10 PROFESSOR MEILAENDER: We are not
11 embracing their death as our aim.
12 DR. OUTKA: Right.
13 PROFESSOR MEILAENDER: I mean, just as a
14 hypothesis, might that not be what someone would
16 DR. OUTKA: They certainly could reply,
17 but the result of that is this peculiar situation of
18 perpetual potentiality, and so the witness looks very
19 marginal to me. It almost looks like it doesn't have
20 very much to do with them.
21 It simply has to do with a refusal to do
22 something that would bear on them, but at that point -
23 - and I would agree that my application of nothing is
24 lost, and it might have a slightly consequential sound
25 to it there.
1 But I would be willing to risk speculating
2 about consequential steps there if there was something
3 to be done that might do some third-parties good.
4 But in any case, back to your excellent
5 example. Yes, I would have to say that I would have
6 to be careful, and if the logic of the position
7 involved my saying that there would be some even
8 stronger case for doing something before the infant
9 died, then I would have to address that and modify the
10 position so that that consequence was not allowed.
11 How I would do that is a nice question,
12 but I think I probably could devise a way to do it
13 that would not be unlike these other ways that I have
14 tried to devise of saying, look, this is a very
15 special case, this class of perpetual potentiality
17 And it is not to be generalized from to
18 allow nothing is lost to generally be invoked to
19 harvest organs from the living, or from those whom the
20 government has condemned as criminals, or whatever.
21 I do accept that there is a whole range of
22 those cases that I don't want to allow in, in my use
23 of the nothing is lost principle for the sake of
24 talking about embryos discarded.
25 DR. KRAUTHAMMER: Could I interject?
1 DR. KASS: On this point?
2 DR. KRAUTHAMMER: Yes, on this point, and
3 a suggestion for an answer. And that would be that
4 there is a fundamental moral difference in the status
5 of an embryo and of an anencephalic child.
6 The child is a full human being, and
7 anencephalic or not, a comatose person is a full human
8 being, comatose or not, and we don't tear them apart
9 for their parts.
10 They are inviolable, and so I don't think
11 it is a terribly strong objection. An embryo has an
12 intermediate, if you like, moral status, but certainly
13 is not the moral equivalent of a child or an adult who
14 is in a coma.
15 So I don't think that you open yourself up
16 under your argument, professor, to tearing up people
17 who are in comas or who are anencephalics.
18 DR. OUTKA: I will accept that as another
19 friendly amendment. Thank you.
20 DR. KASS: I have Alfonso next.
21 DR. GOMEZ-LOBO: I'm afraid that I am
22 going to disagree with Charles here, but he knows
23 that. Going to Michael Sandel's point. I would put
24 it in very simple terms.
1 Namely, if you go into a lab and you have
2 an embryo in a dish there, and you would not be able
3 to tell whether it was created for research or for
4 reproductive purposes. There is nothing in the being
6 And what I am trying to do is this, is
7 turn the discussion back to what I think is the key
8 point, namely what kind of being we are dealing with
9 here. There were parts of the paper where you,
10 Professor Outka, seemed to be treating embryos and
11 fetuses as if they were different entities.
12 And I think at a given moment you would
13 talk about these entities and these other entities.
14 And it seems to me pretty common sensical that we are
15 talking about stages. Every fetus was previously an
16 embryo, and an embryo developing naturally will become
17 a fetus.
18 These are names that have been coined for
19 certain periods in the live of what, of a human being,
20 if we are talking about human embryos. Just the fact
21 that we can talk about ovine embryos shows that the
22 world embryo doesn't tell us what sort of thing it is.
23 We need the word human there.
24 Now, if that is the case, then of course
25 the big problem is if we have one human being, and you
1 agree that from conception onwards that we have a
2 human being, then why this "diminution of value" in
3 one stage, and then from then onwards -- I don't know,
4 is there an increasing value?
5 You seem to take implantation as the
6 breaking point, and I have heard that before. Of
7 course, you are familiar with the work of Tom Shannon,
8 I assume, right? You quote him.
9 DR. OUTKA: I cite him in a footnote.
10 DR. GOMEZ-LOBO: Sure. Sure. Now, the
11 real critical question is this. Are Shannon's
12 arguments convincing? Is it the case that there is
13 such a decisive break there that we may -- I think you
14 would be more consistent totally to disregard the
15 value of the embryo, or to say, well, it is part of a
16 human being, and therefore it is equally valuable as
17 that same human being at a different point.
18 Now, I don't know if we want to get into
19 the discussion of potentiality in the individuation.
20 But those would be the key points it seems to me,
21 because if a human being starts its conception, if we
22 have there the basic genetic information that is going
23 to carry this organism through the phase in which we
24 find ourselves, then of course I see no reason to
1 think that there might be less value at that point
2 than at another point.
3 In a way, it seems to me that people like
4 Robertson are a lot more consistent at times, and say,
5 well, let's respect -- or Mary Ann Warren for that
6 matter, but let's respect them after they are three
7 years old, after they are rationale, or something
8 along those lines.
9 So the point that I am trying to focus in
10 is why or on what grounds establish this magic break
11 point at 14 days?
12 DR. OUTKA: Well, thank you for that
13 question. I actually think your characterization of
14 the position -- well, I would want to offer the
15 following amendments to it, but then let me talk about
16 whether I think I have given anything like adequate
17 arguments for the positions that I take.
18 But the great or the only bright light
19 that I see in this range of possibilities is
20 conception. So, conception is the point at which
21 someone becomes a kind of primordial part of the human
22 race, and an embryo has the genetic wherewithal to
23 become a person just like the rest of us given the
24 right opportunities.
1 So conception is the first and the
2 brightest line for me. Implantation is none of the
3 other subsequent discriminations that I also defend
4 are anything more approximate, but they are
6 So I don't actually make as much of the 14
7 day period as Shannon does. I don't have this big
8 commitment to individuation versus the other. I stay
9 with conception.
10 But I do say that there is approximate
11 discrimination at the point where implantation occurs,
12 because now we can describe this entity as a power
13 under way, a self-developing power under way. You
14 can't say that about the embryo.
15 DR. GOMEZ-LOBO: Why?
16 DR. OUTKA: Because it is not implanted.
17 It isn't yet a self-developing --
18 DR. GOMEZ-LOBO: That's a circular
20 DR. OUTKA: No, it's not. A self-
21 developing power under way means that if left to its
22 own devices will, and if not interfered with, come to
1 No embryo is going to do that prior to
2 implantation. It won't. I mean, that is not
3 circular. With respect, I don't think so.
4 DR. GOMEZ-LOBO: A fetus left to its own
5 devices won't survive either.
6 DR. OUTKA: In one way it will, in the
7 sense that it certainly depends upon the woman, and I
8 have tried to argue that the one person in all the
9 world for at least the first 20 weeks, and that makes
10 the circumstances of pregnancy sui generis in my view.
11 It is a satisfactory analogy that are
12 entirely satisfactory elude us. But nonetheless,
13 there is now a natural process where if the woman
14 doesn't do anything but live normally, that entity
15 will come to term.
16 And that is not a generalization that you
17 can make about the embryo. You can only make it about
18 the fetus. So I do think that there is nonetheless a
20 PROFESSOR MEILAENDER: Leon, may I just
21 ask one question of Gene with respect to his response
22 to Alfonso. Given what you have said, why did you
23 accept Charles Krauthammer's comment as a friendly
24 amendment since you have just -- it seems to me --
25 committed yourself to a very high estimate of the
1 embryo, if not from conception, at least from the time
2 of implantation?
3 DR. OUTKA: Well, then it is no longer an
4 embryo. It is a fetus. There is a --
5 PROFESSOR MEILAENDER: Well, his
6 distinction was at birth, and that was the friendly
7 amendment that you --
8 DR. OUTKA: Well, I know that it was, but
9 the embryo, though it has irreducible value, I want to
10 argue still -- that until it becomes a fetus, it has
11 moral standing, but not the same moral standing that a
12 fetus has.
13 DR. KASS: By fetus, you mean simply
15 DR. OUTKA: I mean implanted. So there is
16 a irreducible value, but not the same kind of moral
17 standing that a fetus has. I try to lay this out.
18 Whereas, equally protectable value, only occurs when
19 it is viable.
20 DR. KASS: Could I intrude myself in this
21 just because I think that we spent most of the time
22 here on the nothing is lost point, and the distinction
23 between using the spare and creating for.
24 But it seems to me, and I am intuiting
25 from the silence of some of our colleagues, whose
1 manner of making a living I am aware of and you are
2 not, but that we might like some help from you on
3 something else in this paper, which actually has to do
4 with the question of the evaluation of the status of
5 the pre-implantation embryo, which is after all
6 central to our business, whether we are talking about
7 cloning for biomedical research, or down the road to
8 embryonic stem cells.
9 So central to your -- I mean, I think if I
10 understood the paper, you make a lot out of -- the
11 reason that you do not regard either abortion or the
12 destruction of embryos as murder, though you regard
13 the embryonic life as having irreducible, but not
14 necessarily, therefore, equal value if I am not
16 And that turns on some notion of
17 potentiality, which you develop richly, and there are
18 people in this room from previous discussion who have
19 used the term embracing it, and others use it
21 You would, I think, make a contribution to
22 our ongoing discussion if you could say a little bit
23 more about that notion, and to do it in a way in which
24 it might be persuasive, and not to the moral
1 theologians in the room, but to those of us who
2 studied some science.
3 Can you help? How does the notion of
4 potentiality, how does it help us think about this
5 thing that we have before us created in vitro if it is
6 not a full person, which if I understand your paper,
7 you don't claim that it is?
8 That seems to be the core of your teaching
9 to us about its value, and if we don't understand
10 that, I think we may miss this. So can you help?
11 DR. OUTKA: Well, I can try, but I'm
12 afraid that I will probably reiterate what is already
13 on the pages. But maybe to refresh our memories, I
14 say that potentiality applies to embryos and fetuses.
15 And I take fetuses first, and I say that
16 potentiality refers to what they are not yet, and also
17 what they are. And I try to keep fairly low flying
18 here, in terms of trying to offer a descriptively
19 accurate characterization of them.
20 They are not yet an equally protectable
21 life because by virtue of this dependence on one
22 person in all the world, and I do make quite a bit of
23 this, and that pregnancy does have this very special
1 Only the woman can help in a certain way.
2 She is strictly non-transferable. There is no one
3 else in the world that can help if she doesn't. Now,
4 in a way that is a natural fact about us, but it is
5 also a very peculiar natural fact, though it is very
7 It is kind of numerically common and yet
8 it is striking in that there aren't precise analogies
9 to it. And I want to argue then that during this
10 early period she is allowed special discretion by
11 virtue of this absolute dependence that one entity in
12 the universe has on her, and only her.
13 But potentiality also refers to what the
14 fetus already is, and what the fetus already is, is
15 this power under way, which I realize has not
16 convinced all of you of its accuracy.
17 But nonetheless the fetus is very
18 connected to the woman, and still totally dependent
19 upon it, but nonetheless again if she lives a normal
20 life, there is a self-developing quality to the fetus,
21 which if simply left alone will result finally in an
22 entity just like the rest of us.
23 That is also a natural fact about it, and
24 it is this peculiar combination of what the fetus is
1 not yet, and yet is, that represents its peculiar
2 status in the world.
3 And so I want to say that to kill it
4 causes it incomprehensible harm, and that is what
5 makes abortion and infanticide so serious, because
6 there is nothing that we can ever do to compensate, or
7 make amends for that action to the entity.
8 But I also then want to argue that embryos
9 are like fetuses with respect to having this reducible
10 value. They have the genetic wherewithal, but they
11 are not yet a power under way.
12 Now, I take it that given the overall
13 assignment that you all have as a council, you want to
14 see whether or not, and especially your scientific
15 colleagues, or members of the council have any
16 reactions to that with respect to its scientific
17 adequacy, because that is part of your assignment, is
18 to get clearer on that.
19 So I would ask any of you who care to, to
20 comment on whether you think that is a useful
21 description, or wildly inaccurate, or somewhere in
23 DR. KASS: Does someone want to join on
24 that? I mean, there are people still on the queue,
25 and I jumped slightly. The question of potentiality
1 came up here, and I know that it would be a shame if
2 you left without our having a chance to address that,
3 because it seems to be part of the case for the moral
4 work that we had here. Paul.
5 DR. MCHUGH: Well, just a moment on your
6 question of potentiality. I want again to underline
7 something that the professor said. He said that this
8 has the potential if left alone.
9 Well, that of course doesn't apply to, for
10 example, the human development from somatic cell
11 nuclear transplant. You have to do even more to it
12 than just produce it to get it to be human.
13 And I just wanted to make the point that
14 sometimes potentials depend upon further human
15 actions. And the council knows why I am fussing about
16 this, but I want to be sure that I heard you correctly
17 when you said the potential here is if left alone,
18 this entity will follow a course with --
19 DR. OUTKA: Well, you are perfectly right,
20 but that applies to fetuses.
21 DR. MCHUGH: Yes.
22 DR. OUTKA: It does not apply to embryos.
23 I mean, that is the difference between the two as far
24 as I can see. If you don't do something in addition
1 to an embryo, i.e., implant it, it will never be a
2 power under way.
3 DR. KASS: Bill Hurlbut, and then -- well,
4 are you going to speak to this particular point about
5 the science?
6 DR. HURLBUT: Yes. The first thing is
7 that I think we need to come to the point of using the
8 same terms. Scientifically speaking, at least in
9 current literature, the term embryo is used for the
10 first eight weeks of development.
11 But I sense that you are using it pre-
12 implantation and then --
13 DR. OUTKA: Yes, I am. But I think that
14 has almost become in a way a de facto use. Do you
15 have a sense of that as well?
16 DR. HURLBUT: They are not using a term --
17 people are using a term, and Elizabeth suggested that
18 we use this in various contexts, pre-implantation
19 embryo, or pre-embryo, but that actually has its
20 historical derivation from the term pre-implantation
22 And scientifically speaking, an embryo is
23 from conception until 8 weeks. There has been a
24 little fuzzing over the history of it. But basically
25 the distinction that is trying to be put in place
1 there scientifically is that approximately 8 to 10
2 weeks the organization is set, and it is not just
3 getting bigger after that, but it is much more like
5 The early development of form and
6 organization are taking place. One little scientific
7 comment and then I want to ask you a question. I
8 personally don't understand why you feel that in a
9 natural setting at least the pre-implantation embryo
10 has a different moral status than the implanted
12 The fact is that the pre-implantation
13 embryo is drawing nourishment from its mother, and as
14 is evident from the varied result that you get from
15 putting it into a different medium for a while --
16 larger offspring, for example, and more twinning, or
18 And so I can't quite see why that really
19 makes a difference. But that might be the wrong point
20 to address. What I would really like to know -- and
21 this is a very vexing question to me. I have sat in
22 this council now for -- this is the third meeting, and
23 every meeting the issue of potential versus actual,
24 and accrued, or accumulated status keeps coming up.
1 And I feel the good intentions of those
2 who bring it up, and I got in a little discussion with
3 Mike Gazzaniga about this the first week. I felt the
4 weight of it when Janet Rowley said it several times.
5 I keep wanting to know, and wanting to ask
6 of other people why they assign a particular
7 characteristic of accrual as being the moment of
8 implicit dignity; and why the various sides of this
9 equation can't find some meeting point.
10 So I would really like -- I would
11 personally very much value an exchange between you and
12 somebody at least on this panel, or on this council,
13 who is taking a position of accumulated or accrued
14 personhood, or something of that nature. Do you
15 understand what I am getting at?
16 DR. OUTKA: Well, I think so, but let's be
17 sure I do. I mean, my position is -- well, I hope
18 nuanced, but it is hard to pin down, because I both
19 want to attribute irreducible value to any entity
20 after conception, and still make as you say some
21 distinction between the embryo and the fetus.
22 And I accept by the way your pervasion
23 that by embryo I mean pre-implantation entity, and
24 that's what I mean. And if there is an acceptable way
1 to refer to that and that makes for clarity, I would
2 happily accept it.
3 And you may be right that the embryo is
4 dependent upon the woman, too, in a way that I ma not
5 fully doing justice to. It is perhaps significant
6 that I am thinking of embryos as potentially in a
7 state of limbo by virtue of in vitro fertilization
9 I mean, that has made me more aware of
10 implantation as a kind of stage that is discrete in
11 some ways. So I may be overdoing that. You are
12 certainly right that unless we are talking about
13 embryos created that way, or conceived that way
14 rather, we are not talking about an entity that is not
15 also dependent like a fetus is on the woman.
16 But now let's go to your basic concern,
17 and maybe you had better repeat that for me, because I
18 am not sure that I do have it clearly, and it is
19 clearly an important point to you and to some others,
20 and I want to promote whatever I can by way of clarity
21 about your ongoing discussions.
22 DR. HURLBUT: Well, I would really, really
23 like personally to hear a good deep discussion on the
24 issue of the moral significance of potential.
1 And I don't know if it is too much to ask
2 for specifically from one of my colleagues. For
3 example, if Mike Gazzaniga would actually jump in here
4 and engage this, because a lot hinges on this subject.
5 And a few of us are deeply enough trained
6 philosophically to know the real or the deep thoughts
7 on what this term so factual and potential actually
9 DR. OUTKA: Well, I don't think that even
10 the philosophers, however deeply trained they are,
11 have come to any agreement. This is why in a way I
12 felt more emboldened just to say, look, whatever
13 position you take on this status of the embryo and the
14 fetus are going to have major implications for a
15 position that you take on stem cell research.
16 But there is so much disagreement all the
17 way down the line, and yet those disagreements matter
18 so much, I am going to tell you what my own views are.
19 Now, I don't defend them altogether, and
20 that goes back to something that came up earlier.
21 There is a booklet in which I talk about abortion,
22 where I defend them a bit more.
23 But some of that defense is still to come,
24 but nonetheless I think I am clear now on the general
1 lines of the argument, even though I haven't fully
2 justified all the parts of it.
3 DR. KASS: Let me say -- and because there
4 are people in the queue, and we are moving toward the
5 end of this session, I want to let the people who have
6 asked to speak, to give them a chance.
7 Could I simply say that this question of
8 either absolute or prima facie, were tied to something
9 actual or potential, it is not going to go away. And
10 that we had better put it on the agenda for ourselves.
11 Lots of people had a stake in this
12 discussion, and I think Professor Outka has in fact,
13 if we revisited those 3 or 4 pages of the paper. He
14 has given us something to chew on, but I suggest that
15 we perhaps bracket it for now.
16 I just wanted to highlight it as
17 important, and unless someone really wants to join in
18 on and solve this one, let me suggest that we take the
19 people who are waiting.
20 And let's try to do this in about 10
21 minutes, and then break. I have Robby, Frank, Janet,
22 Michael, and Rebecca. That is rather long for the
23 time that we have, but let me ask for a certain
24 concision if I might. Who was the first? Robby?
1 PROFESSOR GEORGE: Thanks, Leon. Well, I
2 will then lay aside the discussion and I was going to
3 go right into the questions that Bill and Alfonso
4 raised, but let me lay those aside right now, because
5 I have another set of questions that will take us back
6 to Michael's original comment and the exchange with
8 And perhaps I will write to Gene with my
9 own two cents about this question about the status of
10 the embryo. But back to the set of distinctions that
11 Michael was calling into question, Michael Sandel.
12 I take it that our position is that once
13 there exists an embryo, who will not be implanted, and
14 whose life will soon end one way or another, then it
15 is either -- and you can tell me which, and I don't
16 know whether it matters.
17 It is either not instrumentalization to
18 disaggregate the embryo for good reasons, or if it is
19 an instrumentalization, it is not a wrongful
21 I don't think you have declared yourself
22 on that, and I don't think that much turns on it, but
23 do you want to say which way you will look at it?
24 DR. OUTKA: it is probably closer to it.
25 I think that is a fine question, and I haven't really
1 thought about it, but I think it is probably closer to
2 not a problematical instrumentalization. I think that
3 is probably what I would say.
4 PROFESSOR GEORGE: Okay. I take it then,
5 if I were going to try to defend a position given that
6 point against my point, I wonder if you would accept
7 this way of defending it.
8 I have to confess in the end that I don't
9 think it can be defended, but I am just trying to see
10 how far it can be defended against Michael's
11 particular critique.
12 Then I think you would have to say that
13 the morally bad thing is in -- and I am sorry to use
14 this language, but I think it is in the spirit of what
15 you have been saying. I am not going to talk about
17 But the morally bad thing is in the
18 intention to create the embryo as an object. That is
19 to say, to create the embryo as a means only. Is that
21 DR. OUTKA: Yes.
22 PROFESSOR GEORGE: So that in way you have
23 distinguished creation by whatever means, and Michael
24 has to be right that the means don't matter, but the
25 creation of the embryo for reproductive purposes from
1 the creation of the embryo again by whatever means for
2 research that would involve its destruction. Yes?
4 PROFESSOR GEORGE: Then I think what has
5 to be defended to make that out would be the idea that
6 embryos created for purposes of reproduction are not
7 created as means or objects, but are created as ends
8 in themselves, even if we know that some of the
9 embryos that are created will in fact not be
10 implanted, and therefore will be subject to licit
11 disaggregation. Right?
12 DR. OUTKA: Yes. That is okay. Licit
13 disaggregation is probably all right, but note the
14 somber quality of this, of accepting all of this.
15 This is mournful stuff. I mean, I mean I am not happy
16 about it.
17 PROFESSOR GEORGE: No, I understand.
18 DR. OUTKA: It is not licit in a kind of
19 pure moral sense at all. It is like we have this
20 aftermath, and what do we do with it.
21 PROFESSOR GEORGE: That it is permissible
22 and that is the key. We may be unhappy about the
23 whole thing, and regret how it came about. Okay.
24 Then the question becomes can we distinguish the
25 treatment of the spares created, again by whatever
1 method, in such a way as to make sense of the idea
2 that despite the fact that they are going to be
3 discarded, and therefore subjected licitly to
4 disaggregation as ins in themselves.
5 And how does that argument go? Does that
6 argument have something to do with the idea that each
7 has a chance of being the one implanted? Does it have
8 to be an equal chance, and that gets us into Jim
9 Wilson's problem about embryo screening?
10 DR. OUTKA: I don't think I have fully
11 worked out what I want to say about that. In part, it
12 is because I see the moral calculations that I am
13 trying to defend as working in response to decisions
14 made by others, which I don't necessarily either
15 rejoice over, or even approve, but where I am
16 nonetheless forced to now deal with them.
17 And what it is maybe licit to do to them.
18 I mean, there the status of fetal cadavers would be a
19 sort of -- well, the use of fetuses terminated in
20 abortion decisions would have a similar kind of status
21 for me, where I am deliberating about things where I
22 am not wholly happy about this data, but I am going to
23 have to now confront it and make some determinations
24 with respect to it.
1 And I am trying to offer a moral case for
2 doing that. But I think that sometimes the force of
3 some of these questions implies that one is more of an
4 actor with respect to what is being decided about than
5 one is.
6 And I would want to be wary about that,
7 and I think the way that you put that almost hints at
8 that, and I would want to resist it.
9 PROFESSOR GEORGE: Oh, I am willing to
10 grant you that, but it seems to me that then on the
11 other side, by the same terms, we have got Michael's
13 You know, he was not involved in any of
14 this, and he is just facing a batch, or at least one
15 embryo that is now in the condition that objectively
16 from your vantage point renders it legitimate for
18 And he is willing to do it and doesn't see
19 any moral reason not to, because it seems to pass the
20 test that you set out.
21 DR. OUTKA: I said that there were gray
23 DR. KASS: Let me just remind you of the -
24 - I mean, I would still like to get other people on
25 the queue, and so if you could --
1 PROFESSOR GEORGE: I'm sorry, I will --
2 DR. KASS: Well, I mean, could we ask the
3 following? This sounds like a nice dialectic. Would
4 you be willing to put in writing, and Gene, would you
5 be willing to respond, and we share this exchange?
6 PROFESSOR GEORGE: I would be intending to
7 write to Gene about the status of the embryo issue
8 anyway, and we can --
9 DR. OUTKA: That's excellent, but these
10 are very important questions.
11 PROFESSOR GEORGE: Just a final point on
12 where we would go and why I think it is relevant. I
13 mean, I am just wondering if at the end of the day
14 what you have got left to say to Michael as a
15 scientist is really a practical or prudential matter;
16 that simply if you go ahead and experiment or use it
17 to disaggregate these embryos, you will be encouraging
18 other people to do.
19 DR. OUTKA: I am not sure -- I am going to
20 try to assimilate Michael's scientist's case into the
21 general case that I want to make about the appropriate
22 use of discarded embryos. That is what I am going to
23 do with it.
1 I am not going to allow it some kind of
2 independent status that derails the basic distinction
3 that I want to make.
4 DR. KASS: Frank.
5 PROFESSOR FUKUYAMA: Well, I apologize,
6 but I am going to have to leave as soon as you respond
7 to my question, as I have one last class to teach this
9 DR. OUTKA: I won't misinterpret your
10 departure then.
11 PROFESSOR FUKUYAMA: This is in a way a
12 devil's advocate kind of question. But I am struck in
13 these discussions of bioethics often that you begin
14 with a moral rule or principle, and then as we have
15 done, have a very subtle discussion about the
16 application of it.
17 But there is no prior agreement on that
18 principle, and the one here is the Kantian distinction
19 between a means and ends, which we have all been -- I
20 mean, nobody has questioned that basic framework.
21 Now, I personally would much prefer that
22 you be a Kantian than a utilitarian, and so I am not
23 hostile to Kantianism, but it has got a lot of
1 I mean, for one thing, pure Kantianism
2 presupposes a dualistic ontology that I think no
3 natural scientist sitting around this table would be
4 willing to accept.
5 I mean, noumena do not obey the laws of
6 physics. You know, laws of natural causation. But I
7 think also Kantian ethics is a big mess, because if is
8 ethics of intentionality.
9 I mean, I don't really see under Kantian
10 ethics how you can fight a "just" war. I mean, when
11 Douglas MacArthur was a division commander in France,
12 he once said I will give a thousand men to take that
14 I mean, if that is not pure
15 instrumentalization, and every military commander that
16 has ever lived has had to make a decision like that,
17 and if that is not instrumentalization, I don't know
18 what is.
19 And this came up -- I think Mike Gazzaniga
20 brought this question up in kind of our e-mail
21 discussion prior to this meeting, that making the
22 distinction between treating human beings as means and
23 ends just begs a lot of questions as to where you make
24 that distinction.
1 I have heard, for example, people argue
2 that since Kant believed that the noumenal quality had
3 to do with our ability to reason that it is actually
4 only fully adult human beings that deserve that kind
5 of protection.
6 Which means actually that you could
7 experiment on infants, and a lot of other people by
8 those rules. So I just would like to hear you defend
9 why we should start from a Kantian premise rather than
10 some other kind of premise.
11 DR. OUTKA: Well, I mean, my reasons are
12 actually much lower flying than you might fear. For
13 one, it did come up in the literature that I was
15 Doerflinger mentioned it. In his case,
16 and in mine, too, there is a kind of Christian -- but
17 I think you could have some more generally religious.
18 I think you could have some specifically Jewish or
19 other kinds of formulations, too.
20 So it is set in a larger framework, and
21 that is point one. It was handy because it had
22 already been cited, and I was desperate to try to find
23 some ways to tie into what I had already presented for
24 reasons of space.
1 But I don't think that it commits. I
2 don't want to be committed to Kantianism, per se. I
3 want to be committed to the second formulation of the
4 categorical imperative is one potentially felicitous
5 way to identify some things we should continue to care
7 But I will sort of reserve the right to
8 interpret it in my own ways, and also stress its
9 importance for our purposes only with reference to
10 illuminating this, the problematical character of
11 doing something to X in order to, or with Leon's
12 friendly amendment, and as part of our plan to create
13 in order to destroy, or some variant of that.
14 That seems to me to be objectionable, and
15 this was one way to try to make that point. So low
16 flying acceptance, your cautions are very well taken.
17 DR. KASS: Very briefly, Janet, and then
19 DR. ROWLEY: Actually, one of these is a
20 response to Jim Wilson, who unfortunately has stepped
21 out. But I think it is not correct to say that the
22 mother to be walks in and looks at a petri dish and
23 says that I want that egg, and that one, and not the
1 My impression is that is not how it
2 happens, and there is no way at the present time for
3 us to suggest or to screen for hair color or
4 intelligence, or any other features.
5 We can screen for sex, and we can screen
6 for known genetic abnormalities that might actually be
7 relevant based on family history. The other issue
8 that keeps coming up again is we are preserving these
9 eggs in perpetuity.
10 And for me perpetuity is hundreds and
11 thousands of years, and I think that is not what the
12 IVF embryos -- their fate and future is. One question
13 that I personally am sorry that I didn't get a chance
14 to talk to, or ask to John Gearhart, is how long can
15 you really keep frozen embryos and expect them to be
16 viable when you thaw them out.
17 Now, I suspect it is some number of years,
18 but I don't know precisely if these embryos are kept
19 in liquid nitrogen, which is very expensive, and you
20 have to keep replenishing it in the tanks at major
21 costs to someone or some institution.
22 It is also clear that he said that at
23 least in his experience that one does look at the
24 embryos that are developing as a result of a
1 particular in vitro fertilization for a family, and
2 selects those that appear to be the best.
3 And he didn't define exactly best, but
4 presumably either are growing somewhat larger, or have
5 more cells, or whatever features are used.
6 And the leftover ones are not as good, and
7 that they have a much lower efficiency or viability
8 than do the ones that are selected for implantation.
9 So I think for us to say that every single
10 embryo left over from IVF has the potential to go on
11 and develop into a robust embryo fetus and child is
12 probably totally incorrect.
13 And I think that we ought to be a little
14 more careful in how we frame some of these things,
15 because I think we are not taking into account some of
16 the other issues.
17 DR. OUTKA: If you all ever find out that
18 question about perpetuity, and how long that actually
19 is, I would be very pleased to know.
20 DR. ROWLEY: Well, what do you think, Liz?
21 PROFESSOR BLACKBURN: Well, enzyme
22 solutions, which are much, much more biologically
23 simple than -- not only cells, but blastocysts, or
24 stages around them, and enzyme solutions will go "off"
1 as you store then for a couple of years, even with
2 care and liquid nitrogen.
3 So there must be some sort of half-life,
4 and so it is maybe a few years. I honestly don't know
5 from IVF clients how that is going to be an assist,
6 but just based on the precedent of even less
7 biologically delicate material, I would be surprised
8 if it was more than a few years.
9 DR. OUTKA: That is a very important
10 question. The United Kingdom, I think, discards them
11 more decisively doesn't it?
12 PROFESSOR BLACKBURN: My accent is
14 DR. OUTKA: Sorry.
15 DR. KASS: It is no longer that united.
16 PROFESSOR BLACKBURN: I am jumping ahead
17 to your inference. I don't know. I don't know what
18 the policy is. So I am just speaking from my very
19 direct laboratory experience of delicate biological
20 material, which is much less delicate than these.
21 DR. KASS: Look, we need to break. I want
22 to give Rebecca the last word if I might.
23 PROFESSOR DRESSER: I didn't try very
24 hard, but I was trying to find out the answer to this
25 question, and I did see last year that there was a
1 report of a healthy live birth from an embryo that was
2 stored -- I believe it was 9 years, and they presented
3 it as if this was the longest duration that they were
4 aware of.
5 But obviously it is difficult on how you
6 do the research to find out the answer. I was
7 interested in the fourth point that you mentioned at
8 the beginning, where you were going to focus on four
9 points, and the fourth point was this issue of
10 political and legal context.
11 And you mentioned this issue of whether
12 there should be a different policy for private funding
13 and public funding. And I know that is not really
14 your specialty, but I wondered if you had any thoughts
15 for us on that fourth point?
16 DR. OUTKA: Well, nothing really
17 interestingly beyond what is on those pages. I mean,
18 I am distressed at the amount of liberality out there
19 in the private sector, where it really is just taken
20 as a matter of course that a thousand research flowers
21 may properly bloom out there.
22 And I think that really is making too many
23 decisions by default, but that doesn't help us very
24 much. And I did remark though that I think that a
25 number of people have come to the conclusion that if
1 you try to impose some overall governmental criteria,
2 you are going to get conclusions that certain people
3 regard as too conservative and constraining.
4 And so it is better to leave it alone, and
5 I am not myself prepared to just accept that without
6 further adieu. But much more work would need to be
7 done on that.
8 PROFESSOR DRESSER: But you wouldn't take
9 the step that, well, that your position should be the
10 position that should be our public policy?
11 DR. OUTKA: No, I would not necessarily
12 presume to that, but I am a great admirer actually of
13 Canadian ways of managing their health care. I just
14 have to confess that.
15 And I do note in the last version of this
16 paper that the position I take is actually closer to
17 the recently announced Canadian one than it is either
18 to the more restrictive policies that the United
19 States has, or the more liberal permissive policies
20 that the U.K. has.
21 So on this, or on Canada's attitude
22 towards reproductive technology, and all of that, it
23 seems to me that they have been more responsible than
24 we have.
1 DR. KASS: I want to thank Professor Outka
2 for an excellent paper, and for a very forthcoming and
3 lively discussion, and for all of you for actually
4 sitting patiently through what is a long and for many
5 of us an intellectually challenging and stretching
7 Thank you very much for being with us, and
8 we will take a break for 15 minutes, and then have our
9 last session.
11 (Whereupon, the meeting went off the
12 record for a break at 3:15 p.m.)
13 DR. KASS: Could we come to order? Why
14 don't we begin? I think a few of our members have had
15 to leave either for class or had a conflict for this
16 last session. I think we're just missing Dan Foster
17 at the moment and maybe he -- ah, perfect. Good,
18 thank you.
19 This is a session in which we return to
20 the topic of our last meeting and revisit our project
21 on cloning. The specific questions are the ethical
22 issues of cloning for biomedical research and I would
23 simply remind us of the approach that we have adopted
24 in full recognition that not that we have failed to
25 reach agreement, but we never expected to reach
1 agreement because this is a vexed, moral question
2 where reasonable people put the moral weight in
3 different places, and that our effort is to explore
4 these differences with no expectations that they're
5 going to be overcome, but rather that they can be
7 The aspiration in this discussion and, if
8 you will, on this part of what we eventually produce,
9 a common document owned by us all in the sense that we
10 agree that this is, in fact, a good representation of
11 the state of the question, while preserving and even
12 sharpening our differences so that no position held by
13 any member of council or by some person not in council
14 that deserves to be represented in council isn't given
15 its fullest and fairest expression.
16 We have been proceeding as colleagues, as
17 fallible human beings with a certain, I don't like the
18 term, but it's been used, with a certain kind of
19 epistemic modesty about our own claims, I mean, to
20 encounter thoughtful people who ought to know better
21 than not to agree with us, ought to give us somehow
22 pause and make us a little more humble about where we
23 stand and that we are interested, maybe when we leave
24 this room, we're interested in victory, but at least
25 for the sake of our meetings, we are adopting the
1 pretense we are interested in clarity and wisdom and
2 not simply beating the other side down.
3 I would suggest and so far, I think with
4 some perhaps exceptions, we have tried to recognize
5 that the people with whom we disagree have something
6 vital to defend and if I might be so bold, vital to
7 defend even for us whether we know it or not, and
8 therefore it behooves us to make sure that we don't
9 shortchange ourselves. And one formulation would be
10 to say that it would be -- nobody would want to see us
11 callous to the needs of suffering humanity. Nobody
12 would want to see us cavalier regarding the treatment
13 of nascent life at some stage or other and no one
14 ought to be indifferent to the effects on a society of
15 doing A rather than B, or B rather than A, or C or
16 none of the above.
17 So I want to tell you where I think we
18 stand in this discussion to see whether I'm right in
19 where we stand and then continue to have -- to advance
20 the discussion. The question of the vexed status of
21 this entity, the cloned embryo, we're now back to the
22 cloning topic. It's related, but not identical, with
23 the status of the embryo created by IVF, which will
24 be, I think, central to the question.
1 I want to remind us of something that
2 we've gotten from Stephen Carter in a message to us
3 about the importance of upholding the distinction
4 between what's legal and what's moral, between the
5 realm of what is permissible legally and what is
6 either good or bad, better or worse, noble or base,
7 right or wrong.
8 All too often and perhaps for
9 understandable reasons, the question of permission or
10 ban hovers over the moral conversation, but it's
11 certainly possible that someone might conclude that
12 this activity is morally dubious, but ought to be
13 permitted and there are all other kinds of
14 possibilities. So I would like us, as best we can, to
15 have this conversation still on the moral plane which
16 is where we've had it before.
17 I would also make an observation and this
18 has come also in some of the conversations, that some
19 of us have been adopting the language of competing
20 goods to describe the present situation before us.
21 And I would at least like to put before us that that
22 might be a way of putting the question that is
23 congenial to some, but that there is another way of
24 formulating what's here and might help us understand
25 why this is so intractable.
1 In moral philosophy there is a distinction
2 made between the right and the good in which the good
3 is an object of desire. There are multiple goods.
4 They don't have any kind of absolute standing for us
5 and you can compromise them to get more of one for the
6 sake of less of the other, whereas claims of right or
7 of justice are things which lay down a kind of marker
8 and at least there's a prima facie claim that they
9 should not be violated, that the burden of proof is on
10 someone to show why they should -- why they can't be
11 violated. And I have the sense, at least in some of
12 the previous discussions, that for those people who
13 regard the embryo as either one amongst us or enough
14 like us to be entitled to some kind of irreducible
15 respect, that is not being treated as a category of a
16 good to be preserved, but as a matter of right. And
17 therefore, arguments of that sort are less likely to
18 -- people who hold that view are less likely to want
19 to put that into a pan balance of competing goods, but
20 who want to insist that this is one of those markers
21 like "thou shalt not" because there's something
22 inviolable here.
23 I don't want to shape the discussion, but
24 I at least want to introduce that distinction as
25 possibly being helpful to us and seeing what might
1 seem to be simply a matter if we talk long enough, we
2 can find the right balance, when in fact, for some
3 people this is not a balancing operation at all, but
4 two different kinds of moral discourse.
5 I think that's -- there are other things
6 to be said, but I want to really open the discussion
7 with the following observation. We have tried in
8 staff conversations and in conversations with you all
9 to stake out several moral positions with respect to
10 cloning for biomedical research and while two of them
11 seem to have come to the fore and have commanded at
12 least some support, I suspect that the two might
13 indeed be enlarged to four. And let me state them and
14 see where we are.
15 It seems to me there are two possible
16 grounds for approving or finding morally acceptable
17 cloning for biomedical research and two possible
18 grounds for disapproving. One would be to approve and
19 to let's say approve with eagerness and without
20 qualification because one does not believe that any
21 harm is being done. This would be a view that held
22 that the embryo in question was beneath the status of
23 having any moral worth and I don't want to get into
24 the language of person and things. I'm not sure
25 that's helpful, but it is not the sort of thing that
1 ought to restrain us from use when good might come of
2 it. Let's call it the position of “approve with zeal”
3 or “approve without qualification.”
4 The second would be to recognize that
5 there is something in the embryonic life here that one
6 is at least agnostic about it or one thinks it has
7 some kind of standing, but that one engages in a
8 balancing operation and it approves with humility and
9 is willing to accept some kind of restrictions or
10 restraint on what can be done, recognizes that there
11 is a harm being done to the embryo, but does not
12 regard that as a moral wrong, that is to say, a
13 violation of some stricture of right. This has been
14 put into a balancing operation.
15 A parallel on the side of the disapprove,
16 it seems to me I'm going upwards in scale. You'd have
17 a position that one could call disapprove with regret
18 or has been said, with tears. I'm sorry, the tears
19 belong on the other side. Approve with tears and
20 here, disapprove but with regret, recognizing that
21 there might be certain kinds of benefits had, but
22 making calculations on prudential grounds or on
23 certain kinds of moral considerations about where this
24 might lead, that one decides, on balance, that the
25 goods to be had are not worth the cost of the
1 balancing operation. And there could be the position
2 that would disapprove as a matter of principle and
3 without qualification because it is immoral to treat
4 even the earliest of human embryos as anything but one
5 amongst us, no matter how much good might come from
7 I take it those are four positions that
8 have been heard around the table, not necessarily
9 articulated in those ways. In the intermediate
10 conversations between the last meeting and this one,
11 we've been mostly working in the middle, that is to
12 say, we have -- I'm not exactly sure about that, but
13 we've had expressions of views that look like
14 disapprove with regret and positions that argue for
15 approve, but with humility and the willingness to
16 accept some kind of restraint.
17 I think from some of the correspondence
18 that there are at least some amongst us who believe
19 that their view of this matter is not adequately
20 represented and I think it turns on the question of
21 whether we haven't made all too much fuss about these
22 little 7-day old embryos.
23 Let me see if I have correctly stated
24 analytically where we are and if so, then the question
25 is where we can go to make sure that these viewpoints
1 are properly developed before we actually either try
2 to persuade one another to move from where we now are
3 to some other place or we finally have to choose and
4 come down with what we really think about this.
5 I think I've said both too much and too
6 little, but let that be -- to prime the state of our
7 own discussion. I remind you, cloning for biomedical
8 research, the arguments of course overlap with the
9 question of the embryos used for research, but we're
10 back on our more narrow topic and the larger one is
11 still in the offing though perhaps informed by some of
12 the things we've just been talking about.
13 Comments, questions, arguments,
15 Gil, please.
16 PROFESSOR MEILAENDER: Just very briefly,
17 I just want to note that it's not necessarily a
18 question of whether someone thinks his or her position
19 has been kind of adequately represented in that focus
20 on the middle. For instance, as I recall, one of
21 Frank Fukuyama's comments that he sent in was really
22 questioning whether the approve with humility position
23 was the right representation of the going argument in
24 a way and I, myself, had questioned whether it was
25 really the strongest form of the argument. So it's
1 not -- I think it's not just a question of whether one
2 thinks one's own position is represented, but just
3 where the balance of the argument should lie.
4 DR. KASS: Mike, do you want to get in on
5 this, please?
6 DR. GAZZANIGA: I'll take the bait. I
7 think we should do everything we do with great
8 humility. You realize how often in life you're wrong,
9 it's a good model. But someone with I guess my
10 particular view would not see the need for the
11 preceding two hours of torturous debate of trying to
12 shoehorn into this problem all of the issues that are
13 trying to be shoehorned into us. So I view the embryo
14 by which we mean the blastocyst, either formed by IVF
15 or through somatic nuclear cell transfer as a thing
16 that deserves human respect like all human tissue, but
17 provides me with absolutely no moral dilemma to
18 proceed into biomedical research on it.
19 DR. KASS: Does someone join on that?
20 This is, in fact, I suspect, a not uncommon position.
21 It might even be more common in this body than simply
22 Michael, so could we have some discussion?
23 DR. GAZZANIGA: I guess what I was -- I
24 don't know what other people think and it's up to them
25 to say. But I do like what you've done here which is
1 to broaden the spectrum of response to the question at
3 DR. KASS: Right.
4 DR. GAZZANIGA: And I think that was an
5 important gesture.
6 DR. KASS: Right. Rebecca, please?
7 PROFESSOR DRESSER: This isn't exactly in
8 response to what you were saying, but in thinking and
9 reading about this, it seems to me that people in both
10 1 and 2 categories, the approval categories are
11 affected by some notion of duty to rescue or duty to
12 be a good Samaritan and that it's not just some
13 judgment about the value of the embryo or the
14 viability of the embryo, but it's a moral -- a strong
15 moral feeling that this is what we ought to do to help
16 people who are very ill. And I just wondered if that
17 is a concept worthy of exploring with these two
18 positions, that is, you know the moral philosophy on
19 duty to rescue and when do we have one and what are
20 the considerations that ought to go into determining
21 whether people have a duty not just to refrain from
22 harming, but to actually act to rescue people who are
23 in dire circumstances. So I'll just throw that in.
24 DR. KASS: Let me add one further thing.
25 As you know from the start we have been trying to
1 place our limited moral arguments in the larger
2 context. In the case of cloning for producing
3 children, we tried to put it in the context of human
4 procreation and with the help of some comments from
5 Michael Sandel and others, it's clear that human
6 procreation also means relations between parents and
7 children. It's not just the procreative act. We're
8 trying to put these things -- the right context for
9 this is not just what's the status of the embryo, but
10 the right context for this is what is the vocation of
11 healing and what is, in fact, the mission of
12 biomedical research and these are not simply technical
13 activities. These are activities informed by deep
14 moral commitment and principles and the question is
15 whether these duties are absolute or relative and so
16 on is, of course, for discussion. But I think it's
17 absolutely welcome. We can't simply hash this out
18 over the status of these 100 cells. We also have to
19 think really about the moral principles that guide us
20 here. So that's, I think, very welcome.
21 Elizabeth, please.
22 PROFESSOR BLACKBURN: I've been grappling
23 with this and I think that I'm in position 2, as
24 you've outlined it, approval, but thinking seriously
25 about it and for me a helpful metaphor was thinking
1 about, well, if one were, let's say, there with a
2 blastocyst and you had to do something to keep it
3 alive and then you saw a child drowning, who would you
4 save, if it was a matter of you being in one or the
5 other place and you knew that if you went and helped
6 the child drowning, and I'm using a dramatic example,
7 but if you helped the child drowning, you would have
8 to let the blastocyst die because you couldn't carry
9 out whatever next thing you had to do to keep it
10 alive. So to me, then the choice -- it very much
11 comes down to choosing between two things and making a
12 choice as to what is the more morally imperative, so
13 equating research with its goal of therapy isn't
14 therapeutic benefit and other medical advantages to
15 the idea of saving an existing life in some way that
16 is a fully formed life. So to me, it sort of came
17 down to an either/or. Which one does one weight. So
18 I think your category 2 seems to be fitted by that
20 DR. KASS: Please, Alfonso?
21 DR. GOMEZ-LOBO: I think that was a very
22 nice illustration, actually, and very helpful,
23 although since both are duties of care, I don't think
24 that there is any really serious and deep moral
25 conflict. I think that it's perfectly legitimate to
1 care more for one than the other, if you can't save
2 both. In fact, I would like to take up the -- perhaps
3 the challenge sketched by Rebecca and I think it's a
4 general way of clarifying things or trying to clarify
5 things. I think we do have duties of care, moral
6 duties of care, duties to take action to preserve the
7 goods or to promote them and doubtless, our duties
8 involved in health care are usually of that nature. I
9 mean we make all sorts of effort to say bring our
10 child to the emergency room when the child is sick,
11 etcetera. And of course, that's a very, very
12 important aspect of our moral life.
13 On the other hand, we have duties of
14 respect and we have duties not to harm. Physicians of
15 the older generation perhaps were quite familiar with
16 this, the "first, do no harm" principle. And now
17 these duties have to do with the impermissibility of
18 taking action intentionally that will deprive someone
19 of a good. So in a way it's symmetrical with the
20 other one and the first case we have a duty to
21 promote, protect a good, otherwise would go
22 unprotected and that would make it a moral obligation.
23 Now what happens when there's a conflict
24 between the two because that's what we're talking
25 about. If there were no conflict we wouldn't have
1 much of a problem. Now I don't -- I do agree that
2 some things we have duties of care, but duties of care
3 are usually not that dramatic because if something
4 goes wrong with one of the options, we're really not
5 100 percent responsible for it as in the case of
6 letting the blastocyst die.
7 Now what happens when we have, I'm sorry,
8 did you want to interrupt? Okay. What happens when
9 we have a conflict of care and we have a conflict
10 between care and respect? If I understand it
11 correctly, the tradition of moral philosophy tends to
12 say well, if the duty of respect is such that if you
13 act intentionally, you would be producing an important
14 harm to human good, then that should take precedence
15 over the care.
16 Let me give you an example, perhaps a
17 trivial one, but one which appears in ethics books
18 very often. You have a bandit who has kidnapped 20
19 hostages, an American college woman goes by and this
20 man says look, if you kill one, I'll let the other 19
21 go and of course, that is perceived as a conflict
22 because of course this woman has a duty of care,
23 apparently, to save 19 people. But in order to
24 achieve that goal she has to harm, that is,
25 intentionally kill one person. Since that is the
1 primary action in which she is engaging, it follows
2 that the agent in this case should morally refuse to
3 do it.
4 Now I'm sketching this argument because
5 for me --
6 PROFESSOR SANDEL: Excuse me, would you
7 say that even assuming that you know for sure that the
8 villain will kill the 19 of the 20 if you don't?
9 DR. GOMEZ-LOBO: Yes. Well, first of all,
10 you never know for sure because there's another agent
11 making another decision there. I mean we're not as
12 predictable. Bandits are particularly unpredictable
13 and in most ethics books the bandit is called "Pedro".
15 That says something.
16 PROFESSOR SANDEL: The reason I asked is
17 if that condition did apply, then we would have the
18 nothing is lost principle to argue for killing the
20 DR. GOMEZ-LOBO: Sure. Well, I don't
21 subscribe to the nothing is lost principle by all
23 PROFESSOR SANDEL: Nor do I.
24 DR. GOMEZ-LOBO: Don't sign me on on that
25 one. Plus, I don't think there was a good application
1 of the principle of double effect in our previous
2 discussion. So I'm torn. I'm definitely in group 3
3 here because from the marvelous exposition this
4 morning, I see that, well, we had heard that from Dr.
5 Weissman already. I see how promising all of this is
6 and I see that there are these duties of care, but if
7 -- I know many of you will not concede the "if"
8 clauses of the following sentences, but if embryos are
9 human beings at an early stage of the development, and
10 if we should not intentionally kill innocent human
11 beings, it follows for me that I should not violate
12 the harm principle in this case and that's why I'm on
13 level 3. I do think that this is a morally
14 impermissible action, but I regret it and that's why
15 my question is going to be whether the scientist can't
16 figure out a way of harvesting the stem cells without
17 doing harm and the reply, unfortunately, was no.
18 DR. KASS: Gil Meilaender and then Paul.
19 PROFESSOR MEILAENDER: Well, you're in
21 DR. KASS: No, go ahead. My rudeness and
22 his gentlemanliness give you the floor.
23 PROFESSOR MEILAENDER: Well, a couple of
24 things. I just want to note with respect to the
25 example that Elizabeth gives, I mean I agree with what
1 Alfonso says in the sense that it really brings us
2 back to your comments kicking off this session.
3 Elizabeth's original way of formulating it was a way
4 of thinking about several goods, clearly in
5 competition since you could only save one. Alfonso's
6 way of reformulating it has to do with how he changed
7 it into the question of respect and care, but it's
8 really -- that's a form of the right and the good, in
9 a way. And it's worth noting that there might be
10 other factors that would enter in. I don't know what
11 you'd say to this, but even thinking of it just in
12 terms of the competing goods model, suppose the
13 blastocyst is mine and the drowning child or whatever
14 it was, is somebody else's? Does that count? I mean
15 there are all sorts of factors that enter in here, in
17 So the notion that we've only got one kind
18 of thing, namely stages of development that makes a
19 difference, when we weigh competing goods is not the
20 case, in fact. It's considerably more complicated.
21 We have obligations to try to do good as
22 much as we can, but that means within certain kinds of
23 limits and it means taking account of a whole range of
24 factors, and so it's just worth noting that it's
1 Then the other thing I wanted to comment
2 on was just to come back to Michael's comment that
3 basically what he was saying was he falls into
4 category 1, as you outlined, that there's not really a
5 moral problem here, but that doesn't get us very far
6 to say that because we want to know then what will
7 give us a moral problem. If the early embryo doesn't,
8 at what point would we have a moral problem and why?
9 In order to think about how persuaded we are by that,
10 we need some kind of characteristics or criteria or
11 something that will help us think about it.
12 Otherwise, we only have a position and we don't yet
13 have a kind of a piece of reasoning that we can go to
14 work on. We just need more to do something with it
16 DR. KASS: Michael has in previous
17 meetings, in fact, in the very first meeting if I'm
18 not misremembering, articulated what might be the
19 criteria for moral standing and they were pretty much
20 neurological, but I wouldn't speak for him. Could we
21 draw you out on this because it would be welcome.
22 DR. GAZZANIGA: Sure. One hates to try to
23 answer impossible questions, but you can certainly
24 take approximations. And the approximation that is
25 safe for all concerned who are concerned about your
1 question is that by 14 days the British line in the
2 sand, we're dealing with a system that is brainless
3 and has no capacity for sentience. The brain cells
4 aren't even born and that's pretty raw, elementary
5 biology to -- for me to draw the line at the 14th day
6 and then people come back and give you the
7 potentiality argument and I also said something about
8 that which -- so yes, I'm willing to draw for -- where
9 are we, 2002, that a 14-day line in the sand is a
10 pretty comfortable, keeps you free from thornier
11 issues and I'm going to let someone else draw the next
13 DR. KASS: I'm sorry?
14 DR. GAZZANIGA: I'm going to let someone
15 else draw the next line.
16 PROFESSOR MEILAENDER: Can we have 20 days
18 DR. KRAUTHAMMER: Michael, could I pursue
19 that? Michael, I just want to ask you, forget about
20 the legal issue here. At what point, clearly, you're
21 not at all morally disturbed by working on a
22 blastocyst. At what point in the development of this
23 entity are you personally morally disturbed?
24 DR. GAZZANIGA: Well, you know, let's see
25 how she goes. One step at a time. What's before us
1 in terms of what the scientists are saying we can
2 provide untold remedies, hopefully they can be
3 provided. For the time being, they would be happy and
4 everybody would be happy with the line that I've
5 drawn. The line that I've drawn -- a line. So in 10,
6 15, 20 years, if they come back to the meeting and say
7 look, we need to move that line, how much -- how good
8 their argument is, what people think about it is for
9 another time to be considered. I don't think we have
10 to think that far into the future. I think can we make
11 a comfortable decision in 2002 and I think we can.
12 DR. KRAUTHAMMER: But clearly, what you
13 think about when this organism deserves some respect
14 has to have some influence on your thinking on this, I
15 would assume that you believe a newborn child deserves
17 DR. GAZZANIGA: Of course.
18 DR. KRAUTHAMMER: And I understand that
19 what you're saying of the 7-day-old blastocyst is just
20 a piece of tissue, clearly there's a point at which if
21 you were asked to do the research on this organism,
22 you would say no, and I'm just curious to know what
23 that -- you certainly have thought about this.
24 DR. GAZZANIGA: Well, I don't know if I
1 DR. KRAUTHAMMER: Perhaps you could give
2 it a try.
3 DR. GAZZANIGA: I mean the obvious, from
4 the neurologic base, the obvious fact on the ground is
5 that the organ that is responsible for everything
6 going on in this room is the brain. And the
7 discussions of the issues of human dignity, of human
8 concern, piety, sympathies, those are all constructs
9 of the human mind and so that means you need a brain
10 around to enable those concepts to be used. So one
11 could say that you at least needed the presence of a
12 nervous system and a nervous system doesn't start
13 forming for 4 or 5 weeks and that nervous system, as
14 you know, is impoverished, it's not ready to do the
15 kinds of things we're doing now. And then you start
16 getting into all these unanswerable questions and I
17 just would rather set those aside because I don't have
18 those problems at 14 days.
19 DR. KASS: Do you want to continue?
20 First of all, Michael is very good natured and he's
21 not shy, if I may speak for him. And I think that
22 this, if we're here, let's pursue this a little bit
23 further and see if we can get some clarity on this, if
24 people don't mind. I'm taking advantage of your good
1 DR. GAZZANIGA: We'll see how good natured
2 I remain.
3 DR. ROWLEY: Have you checked with his
6 DR. GAZZANIGA: Sure, go ahead, push me,
7 push me.
8 DR. KASS: Did you want to go further?
9 DR. KRAUTHAMMER: Well, I don't, as a
10 former psychiatrist, I'm guessing here, but I don't
11 think I'm going to succeed. The position I've taken
12 which cut down a lot of trees to publish in The New
13 Republic this week, is based on basically a slippery
14 slope argument. It begins by trying to not assume any
15 intrinsic worth to the 7-day blastocyst, but asking
16 were we to pursue this research, particularly in
17 cloning where you create for the purpose of using the
18 blastocyst and destroying it, what will we become? So
19 I think it is relevant. If you think that it becomes
20 wrong to do the research at a fairly near point after
21 that, and as I understand what you're saying, Michael,
22 it would be at the point where there's beginning of
23 neural development. But you seem to also be saying
24 that you want to draw the line at two weeks, so the
1 slope here, I don't know how slippery it is, but it
2 isn't a big slope between 1 week and 2 weeks.
3 DR. GAZZANIGA: This is where I am in over
4 my head. I like to call up philosophers I know and
5 say can you help me with this slippery slope thing.
7 And they say oh, that's been written about
8 and there's a pro side and a con side. And I say
11 I'll take the con side and we hang up.
12 You can get a driver's license when you're 16, right?
13 Now someone said well, what about 15 years, 11 months,
14 30 days, is that really different than 16? Nah, it's
15 not really different. Well, about 15 years, 11
16 months, and 29 days. Pretty soon with the slippery
17 slope argument you can get down to where babies could
18 be getting driver's license. And of course, that's
19 nonsensical. So what we develop as a species is a
20 capacity for form categories, categories of action,
21 what is generally acceptable. And all I'm suggesting
22 is that we have a category here that we can make a
23 clear decision about and in that way get around the
24 slippery slope analogy which I think can find you in
25 some pretty slippery situations.
1 DR. KASS: Bill?
2 DR. HURLBUT: Here's what it seems to me
3 to come down to. Some people would say that what
4 you're talking about here is not a license to drive,
5 but a license to kill. Now I'm not a lawyer and
6 unfortunately, as I look around the room, it seems to
7 me there aren't any left.
8 Oh, good, right, okay. Rebecca, you're
9 here. But my understanding of the law concerning
10 abortion is that it was not fundamentally a right to
11 take a life. That was a circumstantial secondary
12 effect. The woman had a right of privacy to evacuate
13 her womb of this alien presence that was not, she did
14 not have an obligation to have. Okay? Maybe you can
15 correct me in a second, but let me keep going. So now
16 we have -- you say we have this capacity to form
17 categories. And I want to say parenthetically, I have
18 a lot of trouble figuring this out too, so I'm not
19 trying to attack in saying this, but I'd like
20 clarification on it. You say we have this capacity
21 for categories. Well, one of our major categories is
22 this distinction between a life present or in process
23 and its right to continue or whatever you want to call
24 it. I don't even want to use the language of rights,
1 but this is a major category, this position that you
2 should never take an innocent life in process.
3 Now here's what troubles me about all this
4 from the slippery slope side of the argument. I'm
5 also troubled by the potential argument, but let's put
6 that one aside for the moment and here, Mike, I want
7 to ask you a specific question.
8 So if you really go down and you talk to
9 people about stem cell technology as I've tried to do
10 and by amazing circumstances I know quite a few of the
11 major figures in this field, my assessment of it is,
12 yes, we might be able to find the reagents and bathe
13 the culture in them and get the proper cells we want,
14 but that in fact, we're more likely to get what we
15 want if we were to gestate it for a while, either in
16 utero or artificially of some kind of ectogenesis
17 could be generated.
18 So now what I want to ask you --
19 PROFESSOR WILSON: Mike, what was that?
20 What could be generated? I didn't hear you.
21 DR. KASS: Growth outside, ectogenesis.
22 It grows outside the womb.
23 DR. HURLBUT: It turns out that a lot of
24 what happens in the development process is highly
25 circumstantial. So people working with stem cells are
1 beginning to appreciate how there are these other
2 little micro environments, that if surrounded in a
3 semicircle by one kind of cell which are sending a
4 diffusible agent in in a particular way, then another
5 agent coming from the other side will cause the
6 differentiation, but you can't just bathe it in the
8 The point is that it seems more logical to
9 me that you reasonably could produce more useful
10 therapeutic tissues by allowing gestation or some kind
11 of artificial gestation to go for a while.
12 So I want to take the opposition position
13 for a moment and say why not go beyond 14 days and why
14 restrict ourselves to 14 days now if brain criteria --
15 I think even now my assessment is we could learn a lot
16 and progress faster with the science if we didn't draw
17 that boundary. So I really feel as though that
18 boundary is really just shifting the question of not
19 taking an innocent life to 14 days instead of point of
21 DR. GAZZANIGA: Are you in a position 1,
22 we're haggling price here?
23 DR. HURLBUT: No, because I said I'm
24 prescinding from the question of potential for the
1 moment. So just on your principles, I want to know
2 why we would draw the line at 14 days. And why now?
3 DR. GAZZANIGA: I just told you. It is a
4 line that is comfortable for me to draw. It is a line
5 that would allow the research to go forward. I won't
6 keep repeating myself.
7 DR. HURLBUT: But you said a minute ago
8 that you are comfortable with the fact that until
9 there's a neurologic system which you said was 4 to 5
10 weeks, that you didn't think there was any increased
11 moral standing, so why would you not set that boundary
12 for the moment at 4 to 5 weeks which would make
13 science progress much faster.
14 DR. GAZZANIGA: I don't know enough to
15 know whether you're right or wrong. I leave it to the
16 adjudicating regulatory panels might inform us on
17 that. I don't see this as a crucial point whether
18 it's 14 days or whatever. I'm comfortable with 14
19 days and I'm simply stating my position of 14 days.
20 DR. HURLBUT: I'd also like to comment on
21 -- I'm sorry Mary Ann is not here. Her summation of
22 the last which is relevant here that she seems to be
23 moving towards a conservative position on this issue
24 because of the failure of -- to see any demonstrable
1 products or line of research that are coming out of
2 various stem cell efforts.
3 DR. GAZZANIGA: There's a wonderful article
4 in Science a couple of weeks ago entitled "Some
5 History Should be Repeated." And they review the
6 claims and concerns of people about the recombinant
7 DNA research in 1976 where there was a group of people
8 from Cambridge, Massachusetts where a lot of this was
9 going to go on at MIT that felt funny little organisms
10 were going to ooze out of the MIT labs and envelop
11 Cambridge and people were going to die of these
12 horrible things, yadda, yadda, yadda.
13 And in a similar meeting held in 1970, the
14 late 1970s, they set up this regulatory agency and as
15 a result of now going ahead with recombinant DNA
16 research, none of which was immediately envisioned at
17 the time, we now have, according to this article, 11
18 major drugs that are used in diabetes, hepatitis,
19 acute myocardial infarction, rheumatoid arthritis,
20 stroke serving and saving the lives of millions and
21 millions of people.
22 So the notion that I think some people not
23 scientifically trained don't quite understand is that
24 let the scientists roll. They'll figure it out.
1 They'll figure it out and they're the most
2 conservative people in this room.
3 DR. GAZZANIGA: They beat each other up on
4 a daily basis as to whether what they're saying is
5 correct or wrong. But you can't project into the
6 future what they'll find out. You have to just
7 understand the competencies that they're currently
8 arguing for and then let them go to work.
9 DR. KASS: Dan.
10 DR. FOSTER: I just want to interrupt for
11 one second.
12 DR. KASS: Please.
13 DR. FOSTER: I want to say something a
14 little bit later, but I want to respond to Bill in one
15 sense. We, ourselves, as a council, tend to have
16 different views. We can sort of sense what, as Leon
17 said, and he's come a long way to try to get us into
18 thinking about these things. I think it's critically
19 important in terms of, as Charles would say, building
20 a fence, that we not try to expand what has already
21 been done already when -- outside. I think it's
22 critically important. I myself would be perfectly
23 happy to draw the line at the blastocyst level because
24 I think all the initial basic science can be worked
25 out there and to start moving beyond to the 20 days
1 and so forth. Maybe that would speed up the science.
2 I don't know about that at all. We may find something
3 from the blastocyst in terms of mutation rates and all
4 sorts of things, going to pass away.
5 My own view is I'm starting to get -- but
6 I think it would just be crazy from a practical
7 standpoint to try to say the council wants to come up
8 and extend what we can't even agree on here ourselves.
9 So that's not a moral -- the only reason I'm
10 hesitating to say this, it's not a moral issue, but
11 sooner or later, we have to get off of the high
12 standards of moral things and talk about practical
13 things as well. I think we're starting to talk about
14 very practical things this afternoon. I maybe want to
15 come back to that a little bit, my comments about that
16 a little bit later, but I sure would -- Gil, I always
17 learn things from what you say and write and send me,
18 but I think this time, you're wrong. I think it's
19 wrong to try to expand this thing out, both
20 practically and in terms of trying to get a consensus
21 on some views, our views here in the council.
22 DR. KASS: Let me say I think I
23 understand. I don't want to pretend to have mind
24 reading capacities. But I've been in a number of
25 these discussions and I begin to get to know who's
1 talking. I think what's at issue in this
2 conversation, let me see if I've got it right. Mike
3 Gazzaniga sees no moral difficulty with using
4 blastocysts because he does not regard them as being
5 things of moral worth.
6 He was asked by several people to say
7 well, all right, and he also enunciates a powerful
8 moral principle for going forward, namely, we're going
9 to learn good things and important things and people
10 will benefit from it.
11 So no harm, and great good. What's the
13 Then people want to know well, is there a
14 place where you would have a problem so that if we
15 want to join you we want to know where this train is
16 going and where the limits are which is partly why
17 Charles wants to know, why Gil first of all wants to
18 know what's the ground of this, where is there going
19 to be moral standing and then he gives the argument of
20 nervous system and then the question is well, is the
21 14 days merely a prudential calculation because that's
22 all we need right now and he's willing 15 years down
23 the road to go some place else. I think that's what,
24 in effect, Michael was saying. But there are people
25 who are nervous and who want to hear the principled
1 defense because what they hear here is something like
2 the duty to care and cure being treated as an
3 unqualified imperative beneath which everything else
4 has to submit. And so part of the question for those
5 of us who would care about something, about not doing
6 harm or not violating that which should not be
7 violated, they want to know is there a place.
8 Now other people have used the 14-day
9 marker not as a merely time saving place for the time
10 being, but who really think that 14 days is a
11 transitional point, whether it be implantation -- I
12 don't mean by that just transfer into the woman, but
13 actual physical implantation into the wall of the
14 uterus where you actually have the beginning of a
15 pregnancy, until that time, you don't -- or who want
16 to talk about the primitive streak or who want to talk
17 about the absence of twinning and who try to provide
18 some kind of biological foundation for saying ah,
19 there's something here now not fully one of us, but
20 that's a biologically-based boundary, not in a nervous
21 system, but something else that might count for the
23 So for some of the people in the
24 conversation who want to know, is there something in
25 the nature of things that would give us a guide if the
1 blastocyst is not it yet? I think that's part of the
3 And the other part of the conversation
4 seems to be to test out what actually is the limit of
5 the moral imperative on the side of going forward or
6 are we simply going to say there are sick people out
7 there who need these things and until you come to
8 newborn infants, which I think was the implication of
9 Charles' question, it's ultimately fair game because
10 we can't really, I think, and this is not my -- this
11 was an attempt to summarize what I thought was going
12 on in the conversation. I would add a position of my
13 own. Yes, we are faced with a certain practical
14 decision here and now, but we have to think about the
15 meaning of the kinds of decisions we take here and now
16 for what it legitimates in the future. Yeah, and
17 therefore, we should try and find a good moral
18 foundation as well as being prudential and practically
19 sensible here in trying to reach this and to see
20 whether we can find a place to rest our head, if we
21 can. If not, I think we're in danger of reaching an
22 unprincipled kind of compromise which offers no
23 guidance to those who are going to come after and who
24 might look to this body which was invited to think
25 about this with a view to where this is going,
1 admittedly with uncertain knowledge, but with some
2 power to predict some of the things that might be
3 coming ahead.
4 DR. FOSTER: Leon, I always seem to start
5 these long speeches that I was not speaking to the
6 issue that you posed before us about the moral things.
7 I was talking about a very practical thing and I
8 didn't want to divert off into some other thing. I
9 want to get back to this. I was not making any moral
10 argument at all. I think it's perfectly legitimate to
11 do that. So if you were lecturing me, I was not
12 attempting to make a moral argument.
13 DR. KASS: Excuse me, it wasn't a lecture
14 to you.
15 DR. FOSTER: Well, it sounded like it.
16 DR. KASS: No, sorry, Dan. It was heading
17 off what I thought were going to be people pouncing on
19 DR. FOSTER: I'm so delighted that you're
20 going to take care of me just like the fetus, you have
21 to take care of me, right? Okay, I'm just kidding.
22 DR. HURLBUT: Can I respond, Leon, just to
23 that because I have a very salient point to respond to
25 DR. KASS: Okay.
1 DR. HURLBUT: And it ties to what you're
3 DR. KASS: Okay.
4 DR. HURLBUT: Dan, we were told this
5 morning that fetal primordial neural cells may be
6 useful in Parkinson's disease, right? Okay.
7 DR. FOSTER: Some people believe that.
8 DR. HURLBUT: But let's assume it's right
9 for the moment. Now it's not abstract and it's not
10 way off in the future. It's here and now. So why
11 then would we say, on what principle will we say that
12 a person should not clone himself, gestate or hire
13 somebody or gestate for themselves the embryo up to
14 the age to harvest out those particular very useful
15 cells? This is right here, right now. And yet, the
16 question -- and look, let me make two other points. I
17 am a physician. I really want to see the science go
18 forward very, very, very much. I feel the weight of
19 this. I dream it actually, but I think if we define
20 our principles, we will allow the science to go
21 forward because then we will, for example, if we say,
22 full, generative potential is not acceptable to
23 violate, then we've got the possibility of creating
24 partial generative potential, perhaps, and going
25 around it, the moral problem in a moral way.
1 If we define our larger principles well,
2 it will allow the science to go forward. Otherwise,
3 it's going to get stuck in this morass of conflict.
4 So what I see myself as saying here is something
5 positive to try and set the future in an open way.
6 Moral reality is a fragile reality in any
7 given society and it's something we have to contend
8 with. We can't just ignore it. I think it's harder to
9 set a moral tone of cooperation in a society than it
10 is to make scientific progress. But hopefully, they
11 can go forward together.
12 DR. KASS: Paul McHugh. Thanks for your
13 patience, Paul.
14 DR. McHUGH: Well, I'm going to distract
15 us, I think, from that kind of conversation, but only
16 to reiterate what has been and to emphasize what has
17 been the subject of the conversation between you and
18 me in our epistolary debate in the e-mails.
19 I feel that we will totally submerge into
20 arguments of opinion over actions if we don't agree or
21 come to hear that the somatic cell nuclear transfer
22 clonote is different than the zygote. With Michael, I
23 can partially agree that the clonote should have -- be
24 the subject of study because I think of it as an
25 artifact and I think it different from a zygote.
1 Where I disagree with Michael is that dealing with a
2 zygotic natural program is equally okay. In fact, I
3 wanted to make a point about Mary Ann Glendon. I
4 think she would say her argument was not conservative,
5 but liberal in the sense of wanting to encompass more
6 people under the umbrella of our protection, but the
7 issue of the science here in what we're talking about
8 is an effort to bring science forward in the best way.
9 I want to emphasize what I said in those
10 notes, that is, that the lived experience of
11 scientists making somatic cell nuclear transplants is
12 not that they are creating a new individual, that they
13 are then going to destroy. They are thinking that
14 they are producing tissue that has a particular
15 program and that they're going to use that tissue at
16 some time for the benefit of everyone and I'm
17 approving of that and I want to support that. In
18 fact, I do support it. I believe that the artifact
19 can then be misused if brought on into reproductive
20 cloning, but the fact of it as a different kind of
21 thing permits different kinds of actions towards it.
22 DR. KASS: Do you want to answer publicly
23 one question on this?
24 DR. McHUGH: Yes.
1 DR. KASS: You believe that the clonote is
2 an artifact different in kind because it's different
3 in origin from a zygote, correct?
4 DR. McHUGH: Different in its origins and
5 in its constitution.
6 DR. KASS: And in its constitution. And
7 should that cloned -- should that become cloned at the
8 blastocyst stage and should it be implanted for
9 reproductive purposes and should a child emerge, would
10 that be a human child or would that be an artifact?
11 DR. McHUGH: Well, first of all, those
12 actions should not be done.
13 DR. KASS: But --
14 DR. McHUGH: That human person would be a
15 different person, although you would extend to him
16 because he was tragically created, natural rights to
17 him, but you would see him as a person mistreated and
18 never to have been created.
19 DR. KASS: But not a member of our
21 DR. McHUGH: Not quite a member of our
22 species in the same way, yeah.
23 DR. KASS: Even if capable of reproducing
24 with another member of our species to produce more
25 members of our species?
1 DR. McHUGH: He would be different.
2 DR. KRAUTHAMMER: Is Dolly not a sheep?
3 DR. McHUGH: Dolly is a sick sheep.
4 DR. KRAUTHAMMER: But Dolly is --
5 DR. McHUGH: But this would be a sick
6 person and we would have to take care of him.
7 DR. KRAUTHAMMER: But Dolly is a sheep,
8 sick or not, she's a sheep. I think she's a sheep,
10 DR. KASS: The question has been joined.
11 I don't know if we can sort it out.
12 DR. McHUGH: The point of saying that the
13 clonote has these potentials, that if they are
14 illegally and I would believe that this would be as
15 illegal as slavery or as genocide, that because it has
16 those potentials, that therefore it should be treated
17 as though only those potentials characterize it or
18 that it should be conceived of as only characterized
19 by potential would be an error, an error of logic and
20 an error that would hold back the advancement of
22 DR. KASS: Instead of arguing, let me see
23 if I can put you on the map of positions, the moral
24 positions on this question so we know what homework we
25 have to do.
1 If I now understand you, you do not regard
2 cloning for biomedical research to be a moral problem
3 because the thing that is produced isn't on the human
4 moral scale and therefore --
5 DR. McHUGH: I found it problematic to
6 take your spectrum because I was looking at where I
7 would place myself.
8 DR. KASS: You're in a fifth position.
9 DR. McHUGH: To some extent I hold myself
10 in the place where -- between 1 and 2, okay? I don't
11 think any harm is being done by creating a clonote. I
12 think something good is being done by creating a
13 clonote. But because it is a special kind of new, a
14 kind of biology, I would therefore not permit it to be
15 implanted in a uterus, so maybe therefore I'm treating
16 -- approving with humility in some way because I'm
17 putting limits around what I would do with it.
18 DR. KASS: Okay.
19 DR. McHUGH: You see, if you take the
20 point that the clonote is something different, it's
21 something manufactured rather than begotten, then you
22 would want to study, use its best potentials for human
23 kind and not let its potentials for error and slavery
24 appear, okay?
25 DR. KASS: I owe you a 5-page e-mail.
1 DR. McHUGH: Yes.
2 DR. KASS: You'll get it. Dan, please?
3 DR. FOSTER: I don't want any e-mail. I
4 never write e-mails in these things and the one that I
5 sent I said don't circulate. I'd rather talk
6 personally, but that's okay.
7 Let me make a preliminary remark. Leon
8 said a moment ago in passing, he used a phrase that I
9 think Adam Seligman popularized called epistemological
10 modesty that in the philosophy of studying knowledge
11 that you looked at limits and so forth. I think
12 epistemological modesty means that you believe certain
13 things, but you're modest about these claims and you
14 can be a believer and yet say I'm not really sure.
15 And that's sort of a fundamental fault line here in
16 the discussion.
17 I take seriously and I've been influenced
18 by the people who occupy position 3 here and I'm not
19 willing to agree with Paul that this is just an
20 artifact. I think there's serious issues here that
21 make me nervous.
22 But if you live in what Alfred Shutz
23 called paramount reality, that is being wide awake in
24 the every day world, that's what paramount reality is,
25 it seems to me that common sense shows that a 100-cell
1 human embryo with a potential to ultimately, if
2 everything goes right, becomes a human, has to be
3 taken as serious, as being serious. But it seems to
4 me from this wide awake view that it's different and
5 it doesn't have the same demands for protection and
6 respect as let's say something a little bit later.
7 But I don't know that for sure. And that's why I
8 think one has to occupy what I think I and what I know
9 I occupy which will be position 2.
10 It seems -- I don't -- I'm not comfortable
11 with Rebecca's view that there's some messianic demand
12 to rescue people. I think there are great virtues in
13 suffering and death that come to humanity. I think
14 none of the things that are great in humanity would
15 occur without threat and suffering in the world. If
16 there were not pain, there wouldn't be any need for
17 mercy. If there were not fearful things, there would
18 be no room for courage. One could go through the
19 whole litany of what makes humans different and great
20 or the consequences of risk and suffering in the
21 world. That does not mean that when we're given these
22 brains that we should not try to make the world
23 better. I'm distressed enormously by the fact that
24 the slope of evolution in science appears to be
25 steadily upward and that the slope of evolution for
1 human kindness and beneficence and morality seems
2 almost not to have moved at all.
3 And therefore, I think there's an
4 obligation for those of us who live in this world and
5 want it to be better to try to make wherever we can
6 the world better and if you take -- I may be the only
7 one in the room that really actively takes care of
8 patients and --
9 DR. McHUGH: Hold on.
10 DR. FOSTER: I'm sorry, Paul. He's
11 retired, but he still takes care of them. Okay,
12 forgive me for that.
13 But it is a daunting thing to deal with
14 death. I just lost my long-term colleague. We did 30
15 years of science together. We did good science
16 together and from a glioblastoma multi-form and there
17 are papers, somebody read the PNAS paper last year
18 where you can mark, you can put human glioblastomas in
19 and then just infuse adult neural stem cells in the
20 peripheral blood targets, the glioblastoma, you can
21 take the mass out, but they infiltrate, you can just
22 see pictures. There are two new articles in Nature
23 and Medicine just showing them infiltrating. But
24 these adult cells clamp on to them and you modified
25 them so that you can give a small drug and convert it
1 into a chemotherapeutic agent across the blood-brain
2 barrier. I mean we tried to see if we could do
3 anything for humans like that.
4 So myself, for myself, it's perfectly
5 clear that we ought to try to do better in terms of
6 medicine and the relief of suffering and I don't think
7 the worry, although I'm very worried about it is
8 sufficient to stop that.
9 Here's another point that I think I made
11 DR. McHUGH: Can I ask you a question then
12 about that, Dan?
13 DR. FOSTER: yes.
14 DR. McHUGH: Can I ask you would you take
15 a blastocyst that was naturally formed, taking it out
16 of a uterus, a natural blastocyst and use it in the
17 way you want to use the clonote?
18 DR. FOSTER: No.
19 DR. McHUGH: Why wouldn't you?
20 DR. FOSTER: Because then I would clearly
21 be interrupting a progression, unless nature took it
23 DR. McHUGH: Well --
24 DR. FOSTER: Let me answer it another way.
25 Everybody talks about if you use this, you're going to
1 destroy it. Well, I don't know what the figure is,
2 but 30 to 70 percent of the embryos that form normally
3 are deleted by nature. So what do we say that God is
4 destroying these --
5 DR. McHUGH: Would you put a filter in a
6 uterus and pick up those and then use them the way you
8 DR. FOSTER: I would not.
9 DR. McHUGH: I'm coming back to my
10 artifact which you wish to use as an artifact, but
11 deny. That's what I'm saying here.
12 DR. FOSTER: Well, I guess --
13 DR. McHUGH: You are saying that things
14 which occur naturally you wouldn't use, but things
15 which come out by cloning you would use and I believe
16 that that's because you see an artifactual nature to
17 the clonote.
18 DR. FOSTER: Well, I don't think that's
19 what I believe --
20 DR. McHUGH: Well, would you use a
21 naturally occurring blastocyst formed --
22 DR. FOSTER: You mean while it's in the
24 DR. McHUGH: Yes, when it falls out of the
1 DR. FOSTER: You mean if you take it out
2 of the uterus?
3 DR. McHUGH: yes.
4 DR. FOSTER: No, I wouldn't. I don't want
5 to get into --
6 PROFESSOR SANDEL: that's not the only
8 DR. McHUGH: No, that's not the only
10 DR. FOSTER: I don't want to get into one
11 of these long e-mail exchanges that you and Leon try
12 to do. I'm just trying to make a simple, succinct
13 point and then I'm going to stop right here in just a
14 second, but I do think that we -- that I feel a strong
15 obligation not to stop this and the only thing I was
16 going to say and I argued this with Charles a moment
17 ago, I think if we allowed this to go forward, that is
18 biomedical research, if it turns out that it doesn't
19 work, I agree with Mike, the scientists would be the
20 first to quit and so will biotechnology companies
21 because if it doesn't work, if it's got mutations in
22 it we'll end it. Or, if there are better ways to do
23 this as I think there may well be, it will be
24 abandoned quickly. We've seen that all over in
25 medicine that we abandon things when they go through.
1 So my view is, let's try to learn from this and keep
2 it very limited and I'll pay the price of tears, if
3 that's what it is, if it turns out that in some sense
4 that the universe thinks I've killed a child, which I
5 hope we get rid of that murdering and killing things.
6 I mean there's some sort of an implication that
7 scientists are unethical or immoral or less ethical or
8 less moral than people who are not scientists and I
9 want to try to get away from that. But if that's
10 wrong, then I'll try to tell the universe sometime,
11 I'm sorry, I made a bad mistake. But on the other
12 hand, in the meantime I want to try to see if we can't
13 help a whole lot of humanity with what to me seems to
14 be a different sort of moral problem than the idea of
15 beyond ending a life that's not neurons and other
16 organs and things of that sort.
17 I didn't mean to talk so long. I just was
18 really trying to say that I'm in the position of with
19 a lot of concern as to whether I'm right or not about
21 DR. KASS: Charles?
22 DR. KRAUTHAMMER: I'm a 3 and I'm there
23 for prudential reasons. Mike says and I think if I
24 have the quote correctly, those not trained in science
1 don't understand that what we need to do is let
2 science roll.
3 Well, we let science roll in the 20th
4 century. We got eugenics. We got the Tuskegee
5 experiment. We had such horrors in mid-century that
6 we needed the Nuremburg Code. Humanity hadn't had to
7 write it before, but it had to write it after. So I'm
8 a little skeptical about letting science roll.
9 Scientists are one of the great resources in any
10 society. They do the science, but they don't own the
11 science. And the reason that we're here is because we
12 don't have a guild system in this society, we have a
13 democracy. We don't say to auto makers you know how
14 to make cars, therefore you will determine what safety
15 standards will be in cars. No, it's the nonexperts,
16 it's the lawyers and the Congress who decide what are
17 going to be the safety requirements in cars and that
18 is imposed on the experts who make the cars and that's
19 how we do it in a democracy and that's why we have
20 this council to advise the President and the country
21 on what restrictions might or might not be applied on
22 what is undoubtedly a wonderful enterprise.
23 But we don't have a guild system in which all the
24 rules are made internally, not in a democracy.
1 The reason I'm against research cloning is
2 not because of the reasons underlying position 4 which
3 is somehow attributing a worth to the blastocyst equal
4 or at least comparable to that of a human, but out of
5 a prudential consideration as to what happens if we
7 The first slippery slope and I think an
8 argument that in and of itself would be enough for a
9 person to oppose research of cloning is that I think
10 there can't be any doubt that if we sanction an
11 industry -- and it will become an industry -- for the
12 creation of cloned embryos, it is absolutely
13 inevitable that we will begin to see those embryos
14 implanted and we will have the moral horror of having
15 a cloned embryo in gestation which under penalty of
16 law would have to be destroyed and that is a moral
17 certainty that I think is intolerable. But as I wrote
18 in my piece in The New Republic, that is a little bit
19 too easy. I think it would be reason enough to
20 prudentially oppose research cloning, but let's
21 assume, put it aside. I think there are other reasons
22 and the reasons are that once you start on this, once
23 you start rolling along this road, it will lead us to
24 places where I think that we don't want to go. I may
25 be wrong, obviously nobody knows exactly how we will
1 end up or where this will take us, but I think a
2 prudent society needs to make choices based on past
3 history and some understanding of human nature.
4 The problem, Daniel, is not that the
5 research might fail. The danger is that it might
6 succeed wonderfully and we will then have scientists
7 say as we just heard, give me three more weeks with
8 this embryo. Why not have a fetus where the organs
9 are developed and use them for transplantation rather
10 than have a Rube Goldberg system of growing it into a
11 blastocyst, teasing out stem cells, tweaking them into
12 developing into cell lines. Why not let nature
13 produce with that wonderful machine a fetus and let's
14 strip it apart for its parts? Most of us would say
15 today that is unconscionable. Well, I suspect that if
16 we live in a society where we do this kind of stuff at
17 an earlier level, for a decade or two or three, it
18 will be less unconscionable.
19 In the end, I think the major issue here
20 is that we are crossing a new barrier with research
21 cloning and that is the creation of embryos solely for
22 their use and I'm afraid that once you do that and we
23 create an industry in which this will be the business
24 of that industry, embryo creation, that we will so
25 desensitize ourselves to the use or misuse of this
1 entity that we will end up doing things that we don't
2 want to do and don't want a society to do.
3 I think that prudential argument is one on
4 which we can argue about well, what are the
5 likelihoods of these things happening, but I think we
6 ought to be realistic, that once you start on that
7 road, we will be, as a society, far less able to
8 resist the temptations that today seem obvious that we
9 ought to resist, but tomorrow, probably won't.
10 DR. KASS: Jim Wilson?
11 PROFESSOR WILSON: I've listened for years
12 to Charles and read Charles for years without, I
13 think, disagreeing with a single word he's uttered
14 until today. And my problem is with the slippery
15 slope argument. The slippery slope argument which we
16 hear much of in the literature although it's rarely
17 defined, is kind of a warning sign that's put up on a
18 highway, don't go any further or unknown bad things
19 will happen to you. But rarely is it carried out to
20 show that if you walk past that sign, these unknown,
21 soon-to-be-named bad things will, in fact, happen to
22 you. The slippery slope argument here does have a
23 name as what's going to happen to us if we permit the
24 use of somatic cell transfer for the purposes of
25 creating clones for biomedical research. It is
1 inevitable that we will soon have cloning to make
2 babies and perhaps cloning to produce from fetal
3 organs parts to be used by human beings and after that
4 God knows, perhaps organs taken from babies.
5 That's an argument that can be used
6 against every advance in medical science that has been
7 made that I can think of. We must not invent surgery
8 because the use of the scalpel to take out an appendix
9 will inevitably, on the slippery slope, lead to organ
10 harvesting and the selling of kidneys and livers on
11 the public market. We must not allow neurosurgery,
12 even to cure a terrible tumor because it will lead
13 inevitably to lobotomy. Now, in fact, lobotomies have
14 occurred. And in fact, some instances of organ
15 harvesting have occurred, but the public's horror and
16 the government's horror at these things has quickly
17 shut down those enterprises and penalized, often
18 severely, the people who did it. Or perhaps we
19 shouldn't have automobiles because we will have
20 fatalities. Well, we do have fatalities, but then we
21 balance the value of the automobiles with the value of
22 the fatalities. Or we shouldn't -- you can make an
23 argument about any human innovation and say we must
24 not adopt it because we'll be on the slippery slope
25 and it is, in fact, a Luddite argument, unless you're
1 able to show that sliding down that slope is
3 Now you might be able to say that sliding
4 down that slope is inevitable in the case of cloning
5 because there will be such a huge financial demand for
6 the benefits of cloning that any form of cloning,
7 however benign in original intention, will lead to the
8 worse forms of cloning to satisfy that demand. But
9 from all the scientific testimony I've heard so far,
10 there isn't this huge financial demand and there isn't
11 because nobody has found yet the exact techniques that
12 competent, but ordinary physicians can use to cure
13 these diseases, so that I want us to back away from
14 the prudential or this particular prudential argument
15 because I don't think it's correct unless Charles is
16 in a position to show that the slope is so slippery,
17 so covered with banana oil, that one step past the
18 warning line we have now drawn on the pavement will
19 bring us down into chaos.
20 DR. KRAUTHAMMER: Well, let me give you a
21 recent and empirical example of that slope. The
22 country had a debate on stem cells about a year ago
23 and the major argument by the proponents of stem cell
24 research -- and I was one of them -- was that we are
25 using discarded embryos, everybody understood that,
1 and we were going to bring a benefit from something
2 that would otherwise bring no good. The understanding
3 was, in fact, Senator Frist made the presentation on
4 the floor of the Senate and he established conditions
5 under which he would support stem cell research, the
6 regulations that we ought to institute in support of
7 that research and among them he listed very
8 emphatically that the research would not be done with
9 embryos created for the purpose of using for stem
10 cells. That was what he said.
11 Now and here we are a year later and we're
12 arguing over a technique of cloning which can only be
13 done in a manner in which an embryo is created in
14 order to destroy. So within a year, what we have is
15 the ground shifting on this debate on precisely a
16 point that a year ago we had been assured would be
17 excluded by regulation and by law.
18 PROFESSOR WILSON: The Senator Frist
19 example is a good one, a particularly good
20 illustration of the proposition that Congress doesn't
21 often mean what it says. You could use an even better
22 example with the 1964 Civil Rights Act and Senator
23 Humphrey's assertion to the Senate at large that it
24 would never be used to establish quotas or goals.
25 These things do happen. But the fact that a year
1 later, a year ago or two years ago, whenever Senator
2 Frist spoke, we now find ourselves discussing this
3 subject. It's very different from saying that the
4 subject, once having been discussed and some
5 authorization once having been past, we have now
6 slipped down the slope to the point where we are
7 creating clones for the making of babies and
8 harvesting organs from fetuses.
9 DR. KASS: Janet, did you want to comment?
11 DR. ROWLEY: Well, let me first just
12 respond to Charles because I think though Senator
13 First may have made some comments, I'm sure that
14 anyone in the field of cloning and embryonic stem
15 cells would not have supported his point of view. So
16 it isn't as though we started and we're downslope. I
17 believe that individuals in embryonic stem cell
18 research had already envisioned that, so we haven't --
19 that position has not been changed of the people who
20 are involved in it.
21 I would like to respond to the discussion
22 that Leon framed as we began this session and my
23 points of view are certainly influenced substantially
24 by my view that we are really, we have the potential
25 of being on the threshold of some major biological
1 discoveries that will be of enormous importance, but I
2 qualify that with the same statement I made when we
3 began this discussion in January, that this is a hope
4 and at the present time we have no idea as to how much
5 that hope will actually be successful and that was
6 reiterated and confirmed again by both speakers this
7 morning, that these are very, very, very early days
8 and the promise that many of us see in this kind of
9 research may -- I think it's not fair to say that the
10 promise will not be realized, but I think that it is
11 fair to say that the promise may take a very long
12 time. And I just want to point out that we began the
13 war on cancer in 1970 with the notion that it was all
14 going to be over in 10 or 20 years and we're far from
15 it. We're far from it because we're dealing with very
16 complex systems in cells about which we are woefully
17 ignorant, but I think the part of the research that
18 will be permitted by going ahead with cloning and some
19 of the aspects of experiments with somatic nuclear
20 cell transfer will enlighten us so much that we'll be
21 able to see better how to expand on these in the
22 future. And I would only echo our morning speakers by
23 saying that I think that to ban this kind of research
24 which has the potential for therapy would be a great
1 DR. KASS: Michael Sandel?
2 PROFESSOR SANDEL: I just wanted to pick
3 up on the last small uncharacteristic slip of Charles
4 where he slipped back into the polemical action
5 description to use Professor Outka's phrase of what
6 cloning for biomedical research is. I thought
7 following Paul's and Leon's corrective which Outka
8 accepted, we agreed that there are two possible action
9 descriptions for both of these practices. By both, I
10 mean creation of embryos for reproductive purposes and
11 creation of embryos for purposes of medical research,
12 a charitable description and an uncharitable one. The
13 charitable description in each case describes the
14 action in terms of the end it's aimed at. So in the
15 case of embryos created for reproduction we point by
16 the description to the end. Likewise, in the case of
17 cloning for biomedical research, the end there is the
18 creation of an embryo for the sake of promoting the
19 curing of disease. There is an uncharitable
20 description available equally to both and if we want
21 to compare them, compare the moral status of these
22 practices, we should use either the charitable
23 descriptions of each or the uncharitable descriptions
24 of each. The uncharitable descriptions in each case
1 doesn't refer to the end being aimed at, but instead
2 to the foreseeable, though undesirable effect.
3 So it would be fair to say that with
4 Charles and with Outka's paper that in the case of
5 creating an embryo for the sake of biomedical research
6 to describe that as creating an embryo in order to
7 destroy it, but only in the same sense that we should
8 describe creation of embryos for reproduction purposes
9 as the creation of embryos in order to discard the
10 inevitable extras that will accompany the practice of
11 IVF. So both activities admit of charitable and
12 uncharitable descriptions and if we're going to
13 compare their moral status, we should compare them
14 either under one description, the things they aim at
15 or under the other description, the foreseeable, but
16 undesirable side effects that accompany both.
17 DR. KRAUTHAMMER: Michael, I'm surprised
18 that you also made an uncharacteristic slip when you
19 said the inevitable destruction of the embryos in IVF
20 because you know, as I know, we could, in principle,
21 establish an IVF clinic tomorrow in which you assign
22 only a single embryo to a woman. So you would thereby
23 have a process of IVF where you have no inevitable,
24 indeed, indeed no discarded embryos.
1 On the other hand, in cloning, it is
2 absolutely inevitable that that embryo, because it
3 will be disassembled, will be destroyed.
4 PROFESSOR SANDEL: Well, if the practice
5 of creating embryos for reproductive purposes involved
6 no spares, no extras, then it would have a different
7 moral status and character from the practice we
8 currently have.
9 DR. KASS: Elizabeth?
10 PROFESSOR BLACKBURN: It would be
11 different from natural which, in fact, if anything the
12 majority of embryos naturally are lost and destroyed -
14 DR. KRAUTHAMMER: We'd be improving on
16 PROFESSOR BLACKBURN: That's good.
17 PROFESSOR SANDEL: What the natural case
18 Elizabeth raises is the -- there's also an
19 uncharitable description of natural procreation which
20 would be very odd, which is you're engaging in the
21 inevitable creation of spare embryos that will be
22 sacrificed for the sake of having one that works.
23 PROFESSOR BLACKBURN: Well --
24 PROFESSOR SANDEL: And there's no more
25 warrant for that description than for the contentious
1 version of the description in the cloning for medical
2 research case.
3 PROFESSOR BLACKBURN: Well, I think it
4 might be helpful to return to somewhat more the homely
5 and something Gil said that he said to me, well, would
6 you say the blastocyst, if it were yours versus the
7 child and I think I wouldn't be able to look the
8 parents of the child in the face if I hadn't made an
9 attempt to save the child. And I think that also
10 addresses the issue of should we be trying to do
11 cures, even though we know that they're not inevitably
12 going to work tomorrow, next year, 10 years or 20
13 years. I think we have to try and so I think this
14 question of the fact that we don't have successful
15 answers right now for whether embryonic stem cells or
16 somatic cell nuclear cloning is going to work, I don't
17 think that absolves us from the necessity to try when
18 we see real human disease and suffering that we should
19 try to act on, even though we know we may not be
20 necessarily successful in every attempt.
21 DR. KASS: Gil, and I then I think I would
22 like to put my oar in and I'll give rebuttals, but we
23 should probably wind up. We need a nap before we
24 drink, right?
25 Gil, do you want to comment?
1 PROFESSOR MEILAENDER: Well, just a couple
2 of things quickly. To pick up Elizabeth's point
3 again. The hypothesis was and I think it's worth
4 thinking about, the hypothesis was that you could only
5 save one of the two entities, so that I don't know how
6 we set up this case the way the philosophers do it,
7 but there's a fire and you can go up one stair to save
8 the newborn in the crib who's not yours or you can go
9 up the other stairs to save the blastocyst in vitro
10 that is yours. Okay?
11 DR. KASS: That's a copy of your dead
12 child, if you want to make it --
13 PROFESSOR MEILAENDER: Whatever. It's not
14 -- it's not immediately apparent, kind of, that one
15 choice must be made and that suggests that there are
16 other considerations and it's not just stage of
17 development. The other thing I just wanted to say in
18 response to what Michael -- just -- I mean Gene Outka
19 can sort of take care of himself, but as a matter of
20 interpretation, I think he didn't quite grant what you
21 described him as granting. I think he granted that
22 creating in order to destroy was a tendentious
23 description. He did not grant that the two situations
24 were the same where he had recourse or double effect
25 line which because he did still think that in the
1 description of the one act, the killing was
2 inextricably involved and I take that's really what
3 Charles was getting at. So it isn't in terms of what
4 he was granting, I want to be clear.
5 DR. KASS: Okay, I'm winding up to -- I
6 want to say a couple of substantive things, but come
7 to a procedural suggestion for what we should do next.
8 First, since Jim Wilson began by being surprised that
9 he could disagree with Charles, I'm surprised that I
10 have to disagree with Jim Wilson with whom I've
11 disagreed only once before and he since told me that
12 I've persuaded him, but I'm not going to do it again.
13 PROFESSOR WILSON: Not this time.
14 DR. KASS: The slippery slope, to call
15 something a slippery slope argument is already to put
16 it in a category where you can abstract it and then
17 say you like those arguments or you don't. Rather, it
18 seems to me, it's worth thinking about, not in general
19 in the light of other examples, but to think about it
20 in the context of the particular thing we are talking
22 I think I might have said once before that
23 the reason that arguments about continuity of action
24 are so appropriate in the area that we are here
25 talking about is because development is itself a
1 continuum and the value of the thing being developed,
2 never mind morally, but biologically, increases with
3 development and if it should turn out that tissues
4 down the road are really more valuable for the
5 treatment of the same patients we now want, the
6 argument that's now being made for doing it will be
7 very hard to resist.
8 The real essence of the slippery slope
9 argument is not a prediction, an empirical prediction.
10 It is a question of the logic of justification and
11 it's very important how you somehow justify what
12 you're doing here because if, as in this area, the
13 continuity of development and the continuity of
14 research offers such great promise, you might, without
15 even knowing it, be countenancing the next sort of
16 stages and in the end you will wind up as Bertrand
17 Russell said about pragmatism. It's like a warm bath.
18 It warms up so imperceptibly you don't know when to
19 scream. Eventually, we will get to some place that
20 none of us would want to be and we therefore have to
21 be very careful. It's not a prediction of a certain
22 kind of certainty, although we have seen, I mean five
23 years ago The Washington Post editorialized on this
24 question. No creation of embryos, especially for
25 research -- use these others. The newspapers are no
1 better than the Senators on this and times change and
2 there were no stem cells five years ago. The benefits
3 to be had were less.
4 I think it's very important that we,
5 instead of calling this a slippery slope argument,
6 talk about the question of prudence and if we put it
7 in those terms, then the question is: Is it really
8 prudent to head down this road and I don't think you
9 have to believe that the embryo is a full human
10 person, at least to be worried, not just about what's
11 -- the destruction question. It may be a terrible
12 thing to say in public, but I worry much less about
13 the destruction of the embryos as I worry about the
14 exploitive mentality on the part of not just the
15 scientists, scientists are trying to do good, but of a
16 community that comes to accept as routine, the
17 instrumentalization of nascent life and in which we
18 become sort of desensitized to this. This is not a
19 question about the ontological status of the embryo,
20 but about how we come to regard those earlier stages
21 of our own being. I don't know what they are, but that
22 they're somehow part of a continuity with what we are.
23 Of that, as a biologist and not as a religious figure,
24 I mean I see the continuity.
1 Two other things, just for your thought.
2 I don't want to harangue much longer. The IVF case
3 has been around a number of times, but let me suggest
4 one thing. The fact that there are a lot of embryos
5 lost in normal sexual procreation doesn't settle
6 anything. It doesn't really settle anything. And it
7 seems to me one could say something like this with
8 respect to that in the IVF clinics. When a couple now
9 undertakes to procreate by ordinary sexual means, if
10 they've learned the facts about this, they know that
11 they are saying yes to the sad fact that there will be
12 a lot of loss.
13 That's just the way things are and without
14 going Charles' route about improving God's way, when a
15 couple now goes to the IVF clinic even with the extra
16 embryos, they are saying yes in advance to the sad
17 necessity that some of these embryos are going to be
18 frozen in perpetuity or put to some kind of use.
19 They're simply compressing into one month or into one
20 visible time what in ordinary biology might take
21 months. Well, situations are fairly comparable. I
22 think it is a matter, somewhat different when you
23 undertake to produce the embryos for the purpose of
24 exploiting them for use in which the destruction is --
1 I won't say a minor thing, but it is the deliberate
2 exploitive disposition is what bothers me.
3 Lastly, to Elizabeth, if I might, the
4 lurid cases are wonderful for focusing the mind and
5 the examples, both of the business about the child and
6 the exchange we had last time between Michael Sandel
7 and Robby George about dismembering one's 2-year-old
8 child for the organs and dismembering a blastocyst for
9 the cells spoke, it seems to me, volumes. It seems
10 like for my own sake a knockout case.
11 On the other hand, I'll give you another
12 knockout case and we can wander away and ponder it.
13 Let's imagine that you've got the last couple on earth
14 and a couple of embryos and he has Alzheimer's
15 disease. And the question is, do you sacrifice the
16 embryos for the sake of the cure of the living or do
17 you allow them to be what they in fact are,
18 biologically speaking, the seed of the next
19 generation? We can force ourselves not to look at
20 that because there are so many extra seeds, but if you
21 somehow focus the question and ask, then the merely
22 instrumental use of this seed, even though it doesn't
23 have a nervous system somehow begins to look rather
1 There's a lot there to be quarreled with
2 and I probably abuse the privilege of the chair, but
3 there were a number of things floating around here
4 that only make the subject for me more complicated.
5 What we'll sort out finally is we have to
6 move forward on this. I think if I understand the
7 discussion here and Paul, you and I will have to work
8 out a way to find room for your so far eccentric, that
9 doesn't mean wrong, but unique position in this
10 conversation, whether you want to have a separate --
11 DR. McHUGH: I'm glad you say it doesn't
12 mean wrong. One could be --
13 DR. KASS: On this point we agreed last
14 time that we don't want to simply decide on the basis
15 of the wisdom of the vote of the majority to silence
16 any arguments sincerely held and properly defended.
17 It might very well be that an argument made and held
18 by one person is the best argument and we would
19 deprive our readers of the benefit of having to weigh
21 I'm serious about that.
22 DR. McHUGH: I appreciate that.
23 DR. KASS: And it goes across the board.
24 I think we have to tidy up our work on the ethics of
1 this and move on to the policy questions by the next
2 time we gather.
3 I would like to ask everybody here, if
4 they haven't already, if things that haven't been
5 passed before you don't already speak for you and
6 there are some people who we haven't properly, I
7 think, taken care of. If you would write from 3 to 5
8 pages and if it turns out that the argument is
9 shorter, less, a statement of your view not on the
10 question of ban or no ban, the policy question, but on
11 the question of the morality of cloning for biomedical
12 research and let's have it in two weeks and then we
13 can put this particular part of our discussion in a
14 form that can be circulated for everyone's approval.
15 I hope that's not too onerous. If there's anybody
16 who's writing another paper for another course, I'll
17 give you an extension, but tomorrow morning we meet at
18 8:30 to take up the enhancement discussion and then
19 the regulatory discussion. Thank you for your
20 endurance, your patience, your good will and we're
22 (Whereupon, at 5:33 p.m., the meeting was